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Rewarding effects of hypothalamic self-stimulation altered by unilateral lesions of superior colliculus in rats
352
Brain Research, 215 (1981) 352 358 ~) Elsevier/North-Holland Biomedical Press
Rewarding effects of hypothalamic self-stimulation altered by unilateral lesions of superior colliculus in rats
P. REDGRAVE, P. DEAN and J. ANDREWS* Department of Psychology, University of Sheffield, Sheffield SIO 2TN (U.K.) (Accepted February 12tb, 1981) Key words: self-stimulation - - medial forebrain bundle - - lesion superior colliculus
The effects of unilateral lesions of the superior colliculus were determined on self-stimulation of the medial forebrain bundle. It was found that the lesions had different effects depending upon the precise location of the stimulating electrode: self-stimulation on far-laterally located electrodes was abolished while on more medially placed electrodes this behaviour was enhanced. These data are inconsistent with explanations of intracranial self-stimulation which treat it as a unitary phenomenon. Recent behavioural evidence indicates that in rats the superior colliculus and the ascending dopamine (DA) systems are related in two different ways. On the one hand, the stereotyped licking and gnawing induced by appropriate doses of DA-agonists TM, which has been related to increased DA transmission in the neostriatum 6, is almost abolished by lesions of the superior colliculus~,19,20, 22. A possible anatomical substrate for this effect is the projection from the striatum to the superior colliculus, which relays in the substantia nigra pars reticulata 9,27. In contrast, the locomotor hyperactivity produced by DA-agonists, which has been associated with increased DA transmission in mesolimbic areas so, can be enhanced by collicular lesions19,20,2L The anatomical basis of this effect is unclear, but it seems that DA turnover in the nucleus accumbens (but not the striatum) is increased by lesions of the superior colliculus (Dawbarn and Pycock, personal communication), and that the ventral tegmental area, from which mesolimbic DA fibres originate, receives a collicular inputa7, as. Besides influencing locomotor activity and various forms of stereotyped behaviour, the ascending DA pathways appear also to be involved in intracranial selfstimulationa, 8,30. If so, self-stimulation might also be affected by lesions of the superior colliculus. However, the nature of such an effect is hard to predict, since intracranial self-stlmulation has been associated both with oral behaviours 1,12,13 of the kind that collicular lesions suppress, and with locomotor activity 23 that they can enhance. The present experiment therefore investigated the effects of lesions of the superior colliculus on self-stimulation, obtained from electrodes implanted in the lateral hypothalamus. * Present address: MRC Neuroendocrinology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, U.K.
353 Effective self-stimulation was obtained from 22 rats into which OO ga monopolar electrodes were implanted bilaterally in the area of the lateral hypothalamus (AP: + 0 . 5 to --0.5; lat: 1.75; HV: --8.5) 16. The animals were trained to press a lever that delivered a train of cathodal pulses (0.2 msec, 100 Hz) for as long as it was held down; in this way the animals were able to control the duration of each stimulating pulse train. Wherever possible (n -- 10) self-stimulation was established on both hypothalamus electrodes. After assessing the current-response function(s) for each animal, self-stimulation at intermediate current settings was observed during 10 min testing sessions until the 3 response parameters (presses/10 min, mean duration/press and total time pressed/10 min) had stabilized. Under anaesthetic, unilateral lesions ot the superior colliculus (3 m A anoda! current for 25 sec) were then made through previously implanted stainless steel electrodes (OO ga insect pin insulated except for a cross-sectional area at the tip: AP: --5.0; lat: 1.5; HV: ---4.25) z6. Self-stimulation performance was then observed for up to 12 weeks postoperatively. Within 48 h of receiving unilateral lesions of the superior colliculus 6 of the 22 rats ceased to stimulate on the ipsilateral electrode. This effect persisted for as long as the rats were tested after operation. In 5 of the animals self-stimulation could not be re-established at any of the current levels examined despite repeated testing and attempts at behavioural shaping, while in the sixth, self-stimulation could be obtained reliably at a cuzrent level approximately 3 times that required before operation. None of the 6 rats that ceased to stimulate postoperatively on the ipsilateral electrode stimulated before operation on the contralateral hypothalamic electrode, but one of them began to do so soon after operation. The remaining 16 rats continued to self-stimulate on the hypothalamic electrode ipsilateral to the collicular lesion. However, for the 12 animals that provided sufficient postoperative data points, the characteristics of the behaviour changed significantly after operation (see Fig. 1). The animals pressed the lever more frequently, but each press was shorter such that the overall time spent pressing was reduced. It was our
MEAN PRESSES/ 10 min
MEAN DURATION/ PRESS
MEAN TIME PRESSED/ 10 rain
800
400
1,5 600
300
~ 1.o. z
400
O 200 0.5,
200
100
PRE
POST
PRE
POST
PRE
N POST
Fig. 1. Changes in the response parameters induced by an ipsilateral superior colliculus lesion in those animals which continued to self-stimulate. Differences between the pre- and postoperative means were examined with the Student's t-statistic; the results were for the presses/10 min, tll -- 4.87, P<0.001 ; mean duration/press, tzz = 5.48, P<0.001 ; mean time pressed/10 min, tzz = 3.83, P<0.01.
354 impression that the marked reduction in the average press duration of these animals was not caused by a postoperative increase in the aversive consequences of extended stimulation. Informal observations in which the lever was externally held down for longer than the preferred pulse train duration failed to elicit the normal escape responses. For animals who continued to self-stimulate after operation and who selfstimulated on both hypothalamic electrodes (n -- 10), statistically significant group effects of the unilateral superior colliculus lesion were confined to the ipsilateral electrode, although some individual animals showed some striking changes in selfstimulation contralaterally. Whenever they occurred these changes were similar in nature to those observed with ipsilateral self-stinmlation. Of the rats that continued to stimulate after the first collicular lesion, 10 were given a subsequent lesion of the superior colliculus on the opposite side. In two cases, self-stimulation on the hypothalamic electrode ipsilateral to this second lesion ceased, but all 10 animals continued to self-stimulate on at least one hypothalamic electrode after the superior colliculus had been bilaterally destroyed. To check the adequacy of the lesions, these animals were given two behavioural tests. First, they were observed in a hole-board for 5 min, in which they looked down holes for an average of 1.5 sec (cf. approximately 15-20 sec for normal animals). This is consistent with a previous observation that one-stage bilateral lesions of the superior colliculus abolish headdipping in such a hole-board tesO. Secondly, the rats were given a subcutaneous injection of 8 mg/kg apomorphine. This dose produces intense stereotyped gnawing in normal rats, but not in rats given one stage bilateral lesions of the superior colliculusS,2L Only one of the ten animals tested in the present experiment gave a gnawing score close to the normal mean of 2500 in an automated apparatus (a detailed description of this apparatus will be published separately); the remaining animals scored in the range 0-733. When behavioural testing was completed the animals were killed and their brains were processed according to normal histological procedures 31. Reconstruction of the collicular lesions revealed no obvious differences between those animals that ceased to self-stimulate on the ipsilateral hypothalamic electrode and those that continued (see Fig. 2). However, there were differences in electrode position between the two groups (see Fig. 3). Electrodes on which self-stimulation ceased after ipsilateral collicular damage (either filst- or second-stage lesions) were located significantly more laterally than those on which self-stimulation continued (see Table 1). These results therefore suggest that, contrary to our previous supposition 21, the effects of tectal destruction upon self-stimulation seem to depend upon the precise location of the hypothalamic stimulating electrode. It is tempting to relate this finding to previous observations 5,19,2°,22 that lesions of the superior colliculus suppress oral behaviours associated with increased DA transmission in striatum 6, but enhance the hyperactivity associated with increased DA transmission in the mesolimbic system lo. Since the nigrostriatal fibres tend to course more laterally through the hypothalamus than those of the mesolimbic pathway 7, electrodes at the lateral sites where self-stimulation was suppressed may have principally affected the striatal pathways, whereas electrodes at the more medial sites, at which the
355
A
B
Fig. 2. A : a reconstruction 11 of a superior colliculus lesion f r o m the g r o u p where self-stimulation was abolished. B: a similar reconstruction f r o m t h e g r o u p where self-stimulation continued.
356
5340
5150
4620
4380 /
o
4230
4110
Fig. 3. Sitesit at which self-stimulation ceased (e) or continued (C)) after an ipsilateral lesion of the superior colliculus. Abbreviations: F, fornix; IC, internal capsule; MFB, medial forebrain bundle; MT, mamiilothalamic tract; OT, optic tract.
frequency of stimulation was increased, may have primarily influenced the mesolimbic system. However, the hypothalamus is an area of very great anatomical complexity 24, and the above explanation of the results can only be considered as one of a number of possibilities. Whatever the actual anatomical basis of the present results, they point to the following conclusions. (1) There appears to be a region in the far lateral hypothalamus, close to the optic tract, where self-stimulation is critically dependent upon the integrity of the ipsilateral superior colliculus. It appears to be the colliculus itself that is important, rather than the overlying tissue destroyed by the lesion shown in Fig. 1, because in some animals self-stimulation was abolished by smaller collicular lesions
357 TABLE I Mean co-ordinates ( ± S.E.) of hypothalamic electrodes from animals in which self-stimulation was abolished or continued following an ipsilateral lesion of superior colliculus Electrode co-ordinates 11
Self-stimulation abolished Self-stimulation continued
AP
LAT*
HV
4741 ± 202 4485 ± 75
1.89 ± 0.07 1.35 ~- 0.06
--3.01 4- 0.10 --2.97 4- 0.05
* Difference between means t29 = 4.466; P < 0.001. that caused very little extraneous damage, and because lesions of the overlying tissue alone have little effect on either the oral stereotypy or the hyperactivity induced by D A agonists2L The abolition of self-stimulation at far lateral sites by collicular lesions is particularly striking, in that (a) it is very rare for self-stimulation to be so strongly affected by any lesion s,28, and (b) the effect could not be ascribed to an inability of animals either to perceive or to respond to the self-stimulation lever since 3 animals efficiently self-stimulated on the electrode contralateral to the lesion. (2) Vigorous self-stimulation was obtained in rats with bilateral collicular lesions, who showed very little stereotyped gnawing in response to a high systemic dose of apomorphine. Inasmuch as the effects of collicular destruction upon such oral stereotypy occur because the nigrotectal pathway is damaged, this observation suggests that self-stimulation at the more medial hypothalamic sites may be a DA-related behaviour that does not require the nigrotectal pathway for its expression. This conclusion is consistent with evidence suggesting that self-stimulation from near-lateral hypothalamic sites, but not apomorphine-induced oral stereotypy, can survive damage to substantia nigra pars reticulata15, 26. (3) In this experiment the properties of self-stimulation, at least with respect to the effects of tectal lesions, clearly depended on the location of the stimulating electrode. Other properties of hypothalamic self-stimulation have also been shown to be similarly location dependent2~,2L Such a dependence presents difficulties for any explanation of intracranial self-stimulation which treats it as a unitary phenomenon. This research was supported by SRC Grant B/24707. We thank Iona Hodges for sectioning and staining the brains.
1 Ball, G. G., Micco, D. J. and Berntson, G. G., Cerebellar stimulation in the rat: complex stimulation-bound oral behaviours and self-stimulation, Physiol. Behav., 13 (1974) 123-127. 2 Colpaert, F. C., Van Bever, W. F. M. and Leysen, J. E. M. F., Apomorphine: chemistry, pharmacology, biochemistry, Int. Rev. Neurobiol., 19 (1976) 225-268. 3 Crow, T. J., Catecholamine-containing neurones and electrical self-stimulation: 1. A review of some data, Psychol. Med., 2 (1972) 414-421. 4 Dean, P., Pope, S. G., Redgrave, P. and Donohoe, T. P., Superior colliculus lesions in rat abolish exploratory head-dipping in hole-board test, Brain Research, 197 (1980) 571-576. 5 Dean, P., Redgrave, P. and Pope, S. G., Effects of superior-collicular lesions on apomorphineinduced activity and stereotypy in rats, Neurosci. Abstr., 5 (1979) 332.
358 6 Ernst, A. M. and Smelik, P. G., Site of action of dopamine and apomorphine on compulsive gnawing behaviour, Experientia (Basel), 22 (1966) 837-838. 7 Fallon, J. H. and Moore, R. Y., Cateeholamine innervation of the basal forebrain IV. Topography of the dopamine projection to the basal forebrain and neostriatum, J. comp. Neurol., 180 (1978) 545-580. 8 German, D. C. and Bowden, D. M., Catecholamine systems as the neural substrate for intracranial self-stimulation: a hypothesis, Brain Research, 73 (1974) 381-419. 9 Graybiel, A. M., Organization of the nigrotectal connection: an experimental tracer study in the cat, Brain Research, 143 (1978) 339-348. 10 Kelly, P. H., Seviour, P. W. and lversen, S. D., Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum, Brain Research, 94 (1975) 507-522. 11 K6nig, J. F. R. and Klippel, R. A., The Rat Brain, Williams and Wilkins, Baltimore, Md., 1963. 12 Kooy, D. van der and Phillips, A. G., Trigeminal substrates of intracranial self-stimulation in the brain stem, Science, 196 (1977) 447-449. 13 Kooy, D. van der and Phillips, A. G., Involvement of the trigeminal motor system in brain stem self-stimulation and stimulation-induced behaviour, Brain Behav. Evol., 16 (1979) 293-314. 14 Lyon, M. and Robbins, T., The action of central nervous system stimulant drugs: a general theory concerning amphetamine effects. In W. B. Essman and G. Valzelli, (Eds.), Current Development in Psyehopharmacology, Spectrum, New York, 1975, pp. 79-163. 15 Morelli, M., Porceddu, M. L. and Di Chiara, G., Lesions of substantia nigra by kainic acid: effects on apomorphine-induced stereotyped behaviour, Brain Research, 191 (1980) 67-78. 16 Pellegrino, L. J., Pellegrino, A. S. and Cushman, A. J., A. Stereotaxic Atlas of the Rat Brain, Plenum Press, New York, 1979. 17 Phillipson, O. T., Afferent projections to AI0 Dopaminergic neurones in the rat as shown by the retrograde transport of horseradish peroxidase, Neurosei. Lett., 9 (1978) 353-359. 18 Phillipson, O. T., Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: a horseradish peroxidase study in the rat, J. comp. Neurol., 187 (1979) 117-144. 19 Pope, S. G., Dean, P. and Redgrave, P., Action of amphetamine on hyperactivity produced by lesions of the superior colliculus in rats, Neurosci. Lett., Suppl. 3 (1979) $247. 20 Pope, S. G., Dean, P. and Redgrave, P., Dissociation of D-amphetamine-induced locomotor activity and stereotyped behaviour by lesions of the superior colliculus, Psychopharmacology, 70 (1980) 297-302. 21 Redgrave, P., Andrews, J., Gatfield, J. and Dean, P., Rewarding effects of hypothalamic self-stimulation altered by unilateral lesions of superior colliculus in rats, Neurosci. Lett., Suppl. 5 (1980) $320. 22 Redgrave, P., Dean, P., Donohoe, T. P. and Pope, S. G., Superior colliculus lesions selectively attenuate apomorphine-induced oral stereotypy: a possible role for the nigrotectal pathway, Brain Research, 196 (1980) 541-546. 23 Rompre, P.-P. and Miliaressis, E., A comparison of the excitability cycles of the hypothalamic fibres involved in self-stimulation and exploration, Physiol. Behav., 24 (1980) 995-998. 24 Shiosaka, S., Tohyama, M., Takagi, H., Takahashi, Y., Saitoh, Y., Sakumoto, T., Nakagawa, H. and Shimizu, N., Ascending and descending components of the medial forebrain bundle in the rat as demonstrated by the horseradish peroxidase-blue reaction. I. Forebrain and upper brain stem, Exp. Brain Res., 39 (1980) 377-388. 25 Stephens, D. N. and Herberg, L. J., Catecholamines and self-stimulation: pharmacological differences between near- and far-lateral hypothalamic sites, Brain Research, 90 (1975) 348-351. 25 Stiglick, A. and White, N., Effects of lesions of various medial forebrain bundle components on lateral hypothalamic self-stimulation, Brain Research, 133 (1977) 45 63. 27 Tulloch, I. F., Arbuthnott, G. W. and Wright, A. K., Topographical organization of the striatonigral pathway revealed by anterograde and retrograde neuroanatomical tracing techniques, J. Anat. (Lond.), 127 (1978) 425-441. 28 Valenstein, E. S., The anatomical locus of reinforcement. In E. Stellar and J. Sprague (Eds.), Progress ill Physiological Psychology, Vol. 1, Academic Press, New York, 1966, pp. 149-190. 29 White, N., Brown, Z. and Yachnin, M., Effects of catecholamine manipulations on three different self-stimulation behaviours, Pharmacol. Biochem. Behav., 9 (1978) 603-608. 30 Wise, R. A., Catecholamine theories of reward: a critical review, Brain Research, 152 (1978) 215-247. 31 Wolf, G., Elementary histology for neuropsychologists. In R. D. Myers (Ed.), Methods in Psychobiology, Vol. I, Academic Press, London, 1971, pp. 281-300.
Brain Research, 215 (1981) 352 358 ~) Elsevier/North-Holland Biomedical Press
Rewarding effects of hypothalamic self-stimulation altered by unilateral lesions of superior colliculus in rats
P. REDGRAVE, P. DEAN and J. ANDREWS* Department of Psychology, University of Sheffield, Sheffield SIO 2TN (U.K.) (Accepted February 12tb, 1981) Key words: self-stimulation - - medial forebrain bundle - - lesion superior colliculus
The effects of unilateral lesions of the superior colliculus were determined on self-stimulation of the medial forebrain bundle. It was found that the lesions had different effects depending upon the precise location of the stimulating electrode: self-stimulation on far-laterally located electrodes was abolished while on more medially placed electrodes this behaviour was enhanced. These data are inconsistent with explanations of intracranial self-stimulation which treat it as a unitary phenomenon. Recent behavioural evidence indicates that in rats the superior colliculus and the ascending dopamine (DA) systems are related in two different ways. On the one hand, the stereotyped licking and gnawing induced by appropriate doses of DA-agonists TM, which has been related to increased DA transmission in the neostriatum 6, is almost abolished by lesions of the superior colliculus~,19,20, 22. A possible anatomical substrate for this effect is the projection from the striatum to the superior colliculus, which relays in the substantia nigra pars reticulata 9,27. In contrast, the locomotor hyperactivity produced by DA-agonists, which has been associated with increased DA transmission in mesolimbic areas so, can be enhanced by collicular lesions19,20,2L The anatomical basis of this effect is unclear, but it seems that DA turnover in the nucleus accumbens (but not the striatum) is increased by lesions of the superior colliculus (Dawbarn and Pycock, personal communication), and that the ventral tegmental area, from which mesolimbic DA fibres originate, receives a collicular inputa7, as. Besides influencing locomotor activity and various forms of stereotyped behaviour, the ascending DA pathways appear also to be involved in intracranial selfstimulationa, 8,30. If so, self-stimulation might also be affected by lesions of the superior colliculus. However, the nature of such an effect is hard to predict, since intracranial self-stlmulation has been associated both with oral behaviours 1,12,13 of the kind that collicular lesions suppress, and with locomotor activity 23 that they can enhance. The present experiment therefore investigated the effects of lesions of the superior colliculus on self-stimulation, obtained from electrodes implanted in the lateral hypothalamus. * Present address: MRC Neuroendocrinology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, U.K.
353 Effective self-stimulation was obtained from 22 rats into which OO ga monopolar electrodes were implanted bilaterally in the area of the lateral hypothalamus (AP: + 0 . 5 to --0.5; lat: 1.75; HV: --8.5) 16. The animals were trained to press a lever that delivered a train of cathodal pulses (0.2 msec, 100 Hz) for as long as it was held down; in this way the animals were able to control the duration of each stimulating pulse train. Wherever possible (n -- 10) self-stimulation was established on both hypothalamus electrodes. After assessing the current-response function(s) for each animal, self-stimulation at intermediate current settings was observed during 10 min testing sessions until the 3 response parameters (presses/10 min, mean duration/press and total time pressed/10 min) had stabilized. Under anaesthetic, unilateral lesions ot the superior colliculus (3 m A anoda! current for 25 sec) were then made through previously implanted stainless steel electrodes (OO ga insect pin insulated except for a cross-sectional area at the tip: AP: --5.0; lat: 1.5; HV: ---4.25) z6. Self-stimulation performance was then observed for up to 12 weeks postoperatively. Within 48 h of receiving unilateral lesions of the superior colliculus 6 of the 22 rats ceased to stimulate on the ipsilateral electrode. This effect persisted for as long as the rats were tested after operation. In 5 of the animals self-stimulation could not be re-established at any of the current levels examined despite repeated testing and attempts at behavioural shaping, while in the sixth, self-stimulation could be obtained reliably at a cuzrent level approximately 3 times that required before operation. None of the 6 rats that ceased to stimulate postoperatively on the ipsilateral electrode stimulated before operation on the contralateral hypothalamic electrode, but one of them began to do so soon after operation. The remaining 16 rats continued to self-stimulate on the hypothalamic electrode ipsilateral to the collicular lesion. However, for the 12 animals that provided sufficient postoperative data points, the characteristics of the behaviour changed significantly after operation (see Fig. 1). The animals pressed the lever more frequently, but each press was shorter such that the overall time spent pressing was reduced. It was our
MEAN PRESSES/ 10 min
MEAN DURATION/ PRESS
MEAN TIME PRESSED/ 10 rain
800
400
1,5 600
300
~ 1.o. z
400
O 200 0.5,
200
100
PRE
POST
PRE
POST
PRE
N POST
Fig. 1. Changes in the response parameters induced by an ipsilateral superior colliculus lesion in those animals which continued to self-stimulate. Differences between the pre- and postoperative means were examined with the Student's t-statistic; the results were for the presses/10 min, tll -- 4.87, P<0.001 ; mean duration/press, tzz = 5.48, P<0.001 ; mean time pressed/10 min, tzz = 3.83, P<0.01.
354 impression that the marked reduction in the average press duration of these animals was not caused by a postoperative increase in the aversive consequences of extended stimulation. Informal observations in which the lever was externally held down for longer than the preferred pulse train duration failed to elicit the normal escape responses. For animals who continued to self-stimulate after operation and who selfstimulated on both hypothalamic electrodes (n -- 10), statistically significant group effects of the unilateral superior colliculus lesion were confined to the ipsilateral electrode, although some individual animals showed some striking changes in selfstimulation contralaterally. Whenever they occurred these changes were similar in nature to those observed with ipsilateral self-stinmlation. Of the rats that continued to stimulate after the first collicular lesion, 10 were given a subsequent lesion of the superior colliculus on the opposite side. In two cases, self-stimulation on the hypothalamic electrode ipsilateral to this second lesion ceased, but all 10 animals continued to self-stimulate on at least one hypothalamic electrode after the superior colliculus had been bilaterally destroyed. To check the adequacy of the lesions, these animals were given two behavioural tests. First, they were observed in a hole-board for 5 min, in which they looked down holes for an average of 1.5 sec (cf. approximately 15-20 sec for normal animals). This is consistent with a previous observation that one-stage bilateral lesions of the superior colliculus abolish headdipping in such a hole-board tesO. Secondly, the rats were given a subcutaneous injection of 8 mg/kg apomorphine. This dose produces intense stereotyped gnawing in normal rats, but not in rats given one stage bilateral lesions of the superior colliculusS,2L Only one of the ten animals tested in the present experiment gave a gnawing score close to the normal mean of 2500 in an automated apparatus (a detailed description of this apparatus will be published separately); the remaining animals scored in the range 0-733. When behavioural testing was completed the animals were killed and their brains were processed according to normal histological procedures 31. Reconstruction of the collicular lesions revealed no obvious differences between those animals that ceased to self-stimulate on the ipsilateral hypothalamic electrode and those that continued (see Fig. 2). However, there were differences in electrode position between the two groups (see Fig. 3). Electrodes on which self-stimulation ceased after ipsilateral collicular damage (either filst- or second-stage lesions) were located significantly more laterally than those on which self-stimulation continued (see Table 1). These results therefore suggest that, contrary to our previous supposition 21, the effects of tectal destruction upon self-stimulation seem to depend upon the precise location of the hypothalamic stimulating electrode. It is tempting to relate this finding to previous observations 5,19,2°,22 that lesions of the superior colliculus suppress oral behaviours associated with increased DA transmission in striatum 6, but enhance the hyperactivity associated with increased DA transmission in the mesolimbic system lo. Since the nigrostriatal fibres tend to course more laterally through the hypothalamus than those of the mesolimbic pathway 7, electrodes at the lateral sites where self-stimulation was suppressed may have principally affected the striatal pathways, whereas electrodes at the more medial sites, at which the
355
A
B
Fig. 2. A : a reconstruction 11 of a superior colliculus lesion f r o m the g r o u p where self-stimulation was abolished. B: a similar reconstruction f r o m t h e g r o u p where self-stimulation continued.
356
5340
5150
4620
4380 /
o
4230
4110
Fig. 3. Sitesit at which self-stimulation ceased (e) or continued (C)) after an ipsilateral lesion of the superior colliculus. Abbreviations: F, fornix; IC, internal capsule; MFB, medial forebrain bundle; MT, mamiilothalamic tract; OT, optic tract.
frequency of stimulation was increased, may have primarily influenced the mesolimbic system. However, the hypothalamus is an area of very great anatomical complexity 24, and the above explanation of the results can only be considered as one of a number of possibilities. Whatever the actual anatomical basis of the present results, they point to the following conclusions. (1) There appears to be a region in the far lateral hypothalamus, close to the optic tract, where self-stimulation is critically dependent upon the integrity of the ipsilateral superior colliculus. It appears to be the colliculus itself that is important, rather than the overlying tissue destroyed by the lesion shown in Fig. 1, because in some animals self-stimulation was abolished by smaller collicular lesions
357 TABLE I Mean co-ordinates ( ± S.E.) of hypothalamic electrodes from animals in which self-stimulation was abolished or continued following an ipsilateral lesion of superior colliculus Electrode co-ordinates 11
Self-stimulation abolished Self-stimulation continued
AP
LAT*
HV
4741 ± 202 4485 ± 75
1.89 ± 0.07 1.35 ~- 0.06
--3.01 4- 0.10 --2.97 4- 0.05
* Difference between means t29 = 4.466; P < 0.001. that caused very little extraneous damage, and because lesions of the overlying tissue alone have little effect on either the oral stereotypy or the hyperactivity induced by D A agonists2L The abolition of self-stimulation at far lateral sites by collicular lesions is particularly striking, in that (a) it is very rare for self-stimulation to be so strongly affected by any lesion s,28, and (b) the effect could not be ascribed to an inability of animals either to perceive or to respond to the self-stimulation lever since 3 animals efficiently self-stimulated on the electrode contralateral to the lesion. (2) Vigorous self-stimulation was obtained in rats with bilateral collicular lesions, who showed very little stereotyped gnawing in response to a high systemic dose of apomorphine. Inasmuch as the effects of collicular destruction upon such oral stereotypy occur because the nigrotectal pathway is damaged, this observation suggests that self-stimulation at the more medial hypothalamic sites may be a DA-related behaviour that does not require the nigrotectal pathway for its expression. This conclusion is consistent with evidence suggesting that self-stimulation from near-lateral hypothalamic sites, but not apomorphine-induced oral stereotypy, can survive damage to substantia nigra pars reticulata15, 26. (3) In this experiment the properties of self-stimulation, at least with respect to the effects of tectal lesions, clearly depended on the location of the stimulating electrode. Other properties of hypothalamic self-stimulation have also been shown to be similarly location dependent2~,2L Such a dependence presents difficulties for any explanation of intracranial self-stimulation which treats it as a unitary phenomenon. This research was supported by SRC Grant B/24707. We thank Iona Hodges for sectioning and staining the brains.
1 Ball, G. G., Micco, D. J. and Berntson, G. G., Cerebellar stimulation in the rat: complex stimulation-bound oral behaviours and self-stimulation, Physiol. Behav., 13 (1974) 123-127. 2 Colpaert, F. C., Van Bever, W. F. M. and Leysen, J. E. M. F., Apomorphine: chemistry, pharmacology, biochemistry, Int. Rev. Neurobiol., 19 (1976) 225-268. 3 Crow, T. J., Catecholamine-containing neurones and electrical self-stimulation: 1. A review of some data, Psychol. Med., 2 (1972) 414-421. 4 Dean, P., Pope, S. G., Redgrave, P. and Donohoe, T. P., Superior colliculus lesions in rat abolish exploratory head-dipping in hole-board test, Brain Research, 197 (1980) 571-576. 5 Dean, P., Redgrave, P. and Pope, S. G., Effects of superior-collicular lesions on apomorphineinduced activity and stereotypy in rats, Neurosci. Abstr., 5 (1979) 332.
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