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Amphetamine-induced excitations predominate in single neostriatal neurons showing motor-related activity
Brain Research, 489 (1989) 365-368 Elsevier
365
BRE 23542
Amphetamine-induced excitations predominate in single neostriatal neurons showing motor-related activity John L. Haracz, JoAnn T. Tschanz, Jordan Greenberg and George V. Rebec Department of Psychology, Program in Neural Science, Indiana University, Bloomington, IN 47405 (U.S.A.)
(Accepted 21 February 1989) Key words: Amphetamine; Freely moving rat; Neostriatum; Single-unit activity
Neostriatal single-unit activity was recorded in freely moving rats. A majority (62%) of the 24 recorded neurons were activated during motor behavior such as locomotion (n = 11) or head movements (n = 4). The behavioral response to amphetamine (1.0 mg/kg) was associated with increases (n = 17) or decreases (n = 7) in firing rate. A significantly greater proportion of motor-related neurons were excited by the drug compared to nonmotor-related cells. These results, which confirm the heterogeneity of amphetamine-induced effects in the neostriatum, indicate that the baseline motor-response characteristics of neostriatal neurons may determine their response to amphetamine. Divergent results have arisen from studies of the effects of amphetamine on neostriatal neurons in freely moving rats. Uniformly excitatory responses have been observed in recordings of multiple-unit activity5'15'16 and in the selective recording of single neurons showing locomotor-related activity 18. In contrast, amphetamine has been reported to produce both excitations and inhibitions in samples of neostriatal single units that include both motor- and nonmotor-related cells 4. Methodological issues may account for these findings in that inhibitory responses may not occur as frequently or to the same magnitude as excitatory responses and thus may not be captured by multiple-unit recordings or by recordings of single neurons selected for motorrelated activity. The present study, portions of which have appeared in preliminary form 6, addressed this possibility by quantitating the prevalence and magnitude of responses to amphetamine in a sample of neostriatal neurons that included both motor- and nonmotor-related cells. Male, Sprague-Dawley rats (approximately 400 g) were prepared for single-unit electrophysiology as
previously described 4 and allowed a recovery period of at least 1 week. On the recording day, a varnish-insulated tungsten microelectrode, prepared with an impedance of between 20 and 30 MI2 at 60 Hz 1, was lowered into the anterior neostriatum. Single-unit activity (signal-to-noise ratio of 4:1 or more) was recorded differentially and displayed on an oscilloscope. Neuronal impulses were counted on-line with an amplitude-sensitive spike discriminator, the output of which was routed to a computer (Tandon, PCA) for subsequent analysis. Each animal was placed in an open-field arena (1.3 m e) housed inside a sound-attenuating chamber equipped with a one-way observation window. A videotaping system permitted direct recording of open-field behavior. Firing rates were compared between periods in which the animal was resting quietly and those in which the animal moved about the chamber (e.g. forward locomotion, rearing, head bobbing, and turning). Attempts also were made to manipulate neuronal activity by tactile stimulation of the rat's vibrissae, snout, and body and by provoking the animal to move its head, forepaws, or hindlimbs.
Correspondence: G.V. Rebec, Department of Psychology, Program in Neural Science, Indiana University, Bloomington, IN 47405, U.S.A.
0006-8993/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)
366 Following a period of quiet rest (5-10 min), each animal received a subcutaneous (s.c.) injection of 1.0 mg/kg (free base) D-amphetamine sulfate. Neuronal activity and behavior were monitored continuously for another 30 min to include the peak behavioral response to amphetamine. Mean firing rates of each neuron were calculated for the baseline rest period and for successive 5-min periods after amphetamine injection. Firing rate during baseline rest was defined as 100%, and the amphetamine response was calculated as a percentage of this value for each 5-min period. Upon completion of testing, each animal was anesthetized and a current was passed through the recording electrode to make a small lesion. Following a transcardial perfusion (10% formosaline), the brain was removed, sectioned, and stained with Cresyl violet for histological analysis. A total of 24 recorded single neurons, having a mean baseline firing rate of 3.4 + 1.4 spikes/s (S.E.M.) during quiet resting behavior, included 15 motor-responsive neurons that were activated during locomotion (n = 11) or head movements (n = 4). Many locomotion-related neurons also were activated during a variety of other behaviors such as rearing, grooming, and head movements. The activation typically consisted of bursts of spikes coinciding with characteristic movements, although we occasionally observed tonic activations beginning a few seconds before movement onset and lasting for a short period after cessation of movement. Nine neurons showed activity unrelated to motor behavior. The activity of both motor- and nonmotor-related neurons frequently was altered during the probing of specific body regions (i.e. limbs, face, or dorsum). Two nonmotor-related neurons were activated during the presentation of arousing stimuli, such as a rapidly moving hand or probe near the animal. All neurons displayed biphasic action potentials with peak-to-peak amplitudes of approximately 1000/~V. Amphetamine (1.0 mg/kg)-induced behaviors (i.e. sniffing, locomotion, rearing, and head bobbing) were accompanied by unidirectional increases (n = 17) or decreases (n = 7) in neuronal activity. Both the behavioral and neuronal responses developed gradually 5-15 rain after drug injection. Amphetamine-induced neuronal excitations peaked at 1523
2500,
A
2000.
<~
T 0
T 0-~.~
T "--o
1500. 1000, ~:z ,'7 bJ z
500.
J
0 -------..-~ t':'t
I
I
I
1004 80.
¢rt.d
60. 40 20 o
±
10
• TIME (rain)
"'~ 20
:
.~
30
Fig. 1. Examples of a motor-related neuron excited by amphetamine (A) and a nonmotor-related neuron inhibited by amphetamine (B). Neuron A showed enhanced activity during head movements. Despite showing marked inhibition, Neuron B revealed its identity throughout the recording by maintaining its distinct waveform. D-Amphetamine (1.0 mg/kg) was injected at t = 0 following the determination of baseline firing rate (defined as 100%) during quiet resting behavior. Data points are means + S.E.M. of firing rates derived from a counter output that cycled every 15-20 s. Absent error bar indicates S.E.M. < 15% of the mean.
_ 593% of the baseline rate, whereas inhibitions reached 11.5 + 6.4% of baseline. Amphetamine excited almost all (14 of 15) motor-responsive neurons, but only 3 of 9 nonmotor-related units. This difference in frequency of excitations was significant: ;(e(3) = 12.27, P < 0.01. Fig. 1 depicts examples of the excitatory and inhibitory responses to amphetamine. As shown in Fig. 2, histology revealed that amphetamine-excited, motor-responsive neurons were concentrated in the dorsolateral neostriatum. The only motor-related neuron inhibited by amphetamine showed an interesting behavior-dependent drug response. This neuron was inhibited during most amphetamine-induced behaviors, but activity associated with head movements was enhanced. In the latter respect, this neuron resembled other motor-related neurons: amphetamine typically enhanced activity related to locomotion, rearing, and head movements based on comparisons to firing rates obtained while rats displayed similar, discrete behaviors before amphetamine was injected. Thus,
367
i
ij ,.
-/...
iii
)
,, ,,~
,
'
Br~ma 0.2 mm
Bregma 0.7 mm
Bregma 1.2 mm
Fig. 2. Histologically verified sites of recorded single neurons. Squares and stars represent, respectively, motor- and nonmotor-responsive neurons. Closed and open figures represent, respectively, excitatory and inhibitory neuronal responses to amphetamine. Depicted coordinates of the coronal sections are distances anterior to bregma7. Note that motor-related neurons, which almost exclusively exhibit amphetamine-induced excitations, tend to concentrate in the dorsolateral neostriatum.
amphetamine typically enhanced neuronal activity associated with specific behaviors and increased performance of those behaviors. In agreement with previous studies of rats 4"]8 and monkeys 2, the majority (62%) of neostriatal neurons in our sample showed movement-related activity. Also supportive of previous w o r k 3"18 is our finding that this activity is largely excitatory, although movement-related inhibitions can be observed occasionally 4. Confirming our earlier results in freely moving rats 4"l°A1 and the preliminary results of others 12"~4, the amphetamine behavioral response was associated with both increases and decreases in neostriatal activity. Neurons showing motor-related activity were almost exclusively excited by amphetamine, whereas nonmotor-related neurons usually were inhibited by the drug. The tendency of motorrelated cells to concentrate in dorsolateral neostriaturn is consistent with lesioning studies indicating a role for this region in the control of limb movements 8.9. The present findings may help to clarify previous, apparently contrasting reports of neostriatal neuronal responses to amphetamine in freely moving rats. The greater prevalence and magnitude of excitatory
responses allow an explanation for the uniformly excitatory responses observed in multiple-unit recordings 5'15"16. Such recordings are likely to miss relatively infrequent inhibitory responses among high levels of excitation. Inhibitory responses, almost solely limited to nonmotor-related neurons, also are likely to be missed by selective recordings of motor-related cells 17'18. Though biased toward amphetamine-induced excitations, the selective recordings provided preliminary evidence that the excitations were not secondary to drug-induced behavioral changes 17']8. Drug effects secondary to behavior can be minimized to some extent by examining neuronal activity while the animals display similar, discrete behaviors before and after drug injection. Thus, a primary drug effect, rather than a neostriatal response to behavior, is suggested by our finding that motor-related neurons show amphetamine-induced excitations even when behavioral effects are controlled in the above manner. The possibility that these excitations are a primary drug effect is also supported by the in vitro finding of neostriatal neurons excited by amphetamine 13. Although this issue needs to be examined further, it appears that neuronal responses to am-
368 phetamine in the neostriatum are heterogeneous and that they are systematically related to the baseline motor-response characteristics of individual cells.
1 Ciancone, M.T. and Rebec, G.V., A simple device for the reliable production of varnish-insulated, high impedance tungsten microelectrodes, J. Neurosci. Methods, 27 (1988) 77-79. 2 Crutcher, M.D. and DeLong, M.R., Single cell studies of the primate putamen: I. Functional organization, Exp. Brain Res., 53 (1984) 233-243. 3 DeLong, M.R., Alexander, G.E., Mitchell, S.J. and Richardson, R.T., The contribution of basal ganglia to limb control, Prog. Brain Res., 63 (1986) 161-174. 4 Gardiner, T.W., Iverson, D.A. and Rebec, G.V., Heterogeneous responses of neostriatal neurons to amphetamine in freely moving rats, Brain Research, 463 (1988) 268-274. 5 Hansen, E.L. and McKenzie, G.M., Dexamphetamine increases striatal neuronal firing in freely moving rats, Neuropharmacology, 18 (1979) 547-552. 6 Haracz, J.L., Tschanz, J.T., Ciancone, M.T., Greenberg, J. and Rebec, G.V., Differential effects of haloperidol and clozapine on amphetamine-induced changes in behavior and neostriatal single-unit activity in freely moving rats, Soc. Neurosci. Abstr., 14 (1988) 664. 7 Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, Academic Press, Sydney, 1982. 8 Pisa, M., Motor somatotopy in the striatum of rat: manipulation, biting and gait, Behav. Brain Res., 27 (1988) 21-35. 9 Pisa, M. and Schranz, J.A., Dissociable roles of the rat's striatum conform to a somatotopic model, Behav. Neurosci., 102 (1988) 429-440. 10 Rebec, G.V., Electrophysiological pharmacology of amphetamine. In J. Marwah (Ed.), Neurobiology of Drug
This research was supported by USPHS G r a n t D A 02451 (G.V.R.). We also acknowledge the technical assistance of Dr. Mark Ciancone and Mr. Paul Langley. Abuse, Karger, Basel, 1987, pp. 1-33. 11 Rebec, G.V. and Gardiner, T.W., Regional effects of amphetamine in the neostriatum: single-unit responses in freely moving rats, Soc. Neurosci. Abstr., 11 (1985) 550. 12 Ryan, L.J., Young, S.J., Segal, D.S. and Groves, P.M., Antidromically identified striatonigral neurons are not excited by amphetamine in freely moving rats, Soc. Neurosci. Abstr., 12 (1986) 650. 13 Trulson, M.E. and Arastch, K., Effects of dopamine and amphetamine on mouse caudate neurons recorded in vitro, Eur. J. Pharmacol., 124 (1986) 161-165. 14 Trulson, M.E. and Jacobs, B.L., Effects of D-amphetamine on striatal unit activity and behavior in freely moving cats, Neuropharmacology, 18 (1979) 735-738. 15 Warenycia, M.W. and McKenzie, G.M., Immobilization of rats modifies the response of striatal neurons to dexamphetamine, Pharrnacol. Biochem. Behav., 21 (1984)53-59. 16 Warenycia, M.W. and McKenzie, G.M., Activation of striatal neurons by dexamphetamine is antagonized by degeneration of striatal dopaminergic terminals, J. Neural Transm., 70 (1987) 217-232. 17 West, M.O., Michael, A.J., Chapin, J.K. and Woodward, D.J., A strategy for separating behaviorally-related vs. drug-related changes in unit activity in freely moving rats, Soc. Neurosci. Abstr., 11 (1985) 687. 18 West, M.O., Michael, A.J., Knowles, S.E., Chapin, J.K. and Woodward, D.J., Striatal unit activity and the linkage between sensory and motor events. In J.S. Schneider and T.I. Lidsky (Eds.), Basal Ganglia and Behavior: Sensory Aspects of Motor Functioning, Hans Huber, Toronto, 1987, pp. 27-35.
365
BRE 23542
Amphetamine-induced excitations predominate in single neostriatal neurons showing motor-related activity John L. Haracz, JoAnn T. Tschanz, Jordan Greenberg and George V. Rebec Department of Psychology, Program in Neural Science, Indiana University, Bloomington, IN 47405 (U.S.A.)
(Accepted 21 February 1989) Key words: Amphetamine; Freely moving rat; Neostriatum; Single-unit activity
Neostriatal single-unit activity was recorded in freely moving rats. A majority (62%) of the 24 recorded neurons were activated during motor behavior such as locomotion (n = 11) or head movements (n = 4). The behavioral response to amphetamine (1.0 mg/kg) was associated with increases (n = 17) or decreases (n = 7) in firing rate. A significantly greater proportion of motor-related neurons were excited by the drug compared to nonmotor-related cells. These results, which confirm the heterogeneity of amphetamine-induced effects in the neostriatum, indicate that the baseline motor-response characteristics of neostriatal neurons may determine their response to amphetamine. Divergent results have arisen from studies of the effects of amphetamine on neostriatal neurons in freely moving rats. Uniformly excitatory responses have been observed in recordings of multiple-unit activity5'15'16 and in the selective recording of single neurons showing locomotor-related activity 18. In contrast, amphetamine has been reported to produce both excitations and inhibitions in samples of neostriatal single units that include both motor- and nonmotor-related cells 4. Methodological issues may account for these findings in that inhibitory responses may not occur as frequently or to the same magnitude as excitatory responses and thus may not be captured by multiple-unit recordings or by recordings of single neurons selected for motorrelated activity. The present study, portions of which have appeared in preliminary form 6, addressed this possibility by quantitating the prevalence and magnitude of responses to amphetamine in a sample of neostriatal neurons that included both motor- and nonmotor-related cells. Male, Sprague-Dawley rats (approximately 400 g) were prepared for single-unit electrophysiology as
previously described 4 and allowed a recovery period of at least 1 week. On the recording day, a varnish-insulated tungsten microelectrode, prepared with an impedance of between 20 and 30 MI2 at 60 Hz 1, was lowered into the anterior neostriatum. Single-unit activity (signal-to-noise ratio of 4:1 or more) was recorded differentially and displayed on an oscilloscope. Neuronal impulses were counted on-line with an amplitude-sensitive spike discriminator, the output of which was routed to a computer (Tandon, PCA) for subsequent analysis. Each animal was placed in an open-field arena (1.3 m e) housed inside a sound-attenuating chamber equipped with a one-way observation window. A videotaping system permitted direct recording of open-field behavior. Firing rates were compared between periods in which the animal was resting quietly and those in which the animal moved about the chamber (e.g. forward locomotion, rearing, head bobbing, and turning). Attempts also were made to manipulate neuronal activity by tactile stimulation of the rat's vibrissae, snout, and body and by provoking the animal to move its head, forepaws, or hindlimbs.
Correspondence: G.V. Rebec, Department of Psychology, Program in Neural Science, Indiana University, Bloomington, IN 47405, U.S.A.
0006-8993/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)
366 Following a period of quiet rest (5-10 min), each animal received a subcutaneous (s.c.) injection of 1.0 mg/kg (free base) D-amphetamine sulfate. Neuronal activity and behavior were monitored continuously for another 30 min to include the peak behavioral response to amphetamine. Mean firing rates of each neuron were calculated for the baseline rest period and for successive 5-min periods after amphetamine injection. Firing rate during baseline rest was defined as 100%, and the amphetamine response was calculated as a percentage of this value for each 5-min period. Upon completion of testing, each animal was anesthetized and a current was passed through the recording electrode to make a small lesion. Following a transcardial perfusion (10% formosaline), the brain was removed, sectioned, and stained with Cresyl violet for histological analysis. A total of 24 recorded single neurons, having a mean baseline firing rate of 3.4 + 1.4 spikes/s (S.E.M.) during quiet resting behavior, included 15 motor-responsive neurons that were activated during locomotion (n = 11) or head movements (n = 4). Many locomotion-related neurons also were activated during a variety of other behaviors such as rearing, grooming, and head movements. The activation typically consisted of bursts of spikes coinciding with characteristic movements, although we occasionally observed tonic activations beginning a few seconds before movement onset and lasting for a short period after cessation of movement. Nine neurons showed activity unrelated to motor behavior. The activity of both motor- and nonmotor-related neurons frequently was altered during the probing of specific body regions (i.e. limbs, face, or dorsum). Two nonmotor-related neurons were activated during the presentation of arousing stimuli, such as a rapidly moving hand or probe near the animal. All neurons displayed biphasic action potentials with peak-to-peak amplitudes of approximately 1000/~V. Amphetamine (1.0 mg/kg)-induced behaviors (i.e. sniffing, locomotion, rearing, and head bobbing) were accompanied by unidirectional increases (n = 17) or decreases (n = 7) in neuronal activity. Both the behavioral and neuronal responses developed gradually 5-15 rain after drug injection. Amphetamine-induced neuronal excitations peaked at 1523
2500,
A
2000.
<~
T 0
T 0-~.~
T "--o
1500. 1000, ~:z ,'7 bJ z
500.
J
0 -------..-~ t':'t
I
I
I
1004 80.
¢rt.d
60. 40 20 o
±
10
• TIME (rain)
"'~ 20
:
.~
30
Fig. 1. Examples of a motor-related neuron excited by amphetamine (A) and a nonmotor-related neuron inhibited by amphetamine (B). Neuron A showed enhanced activity during head movements. Despite showing marked inhibition, Neuron B revealed its identity throughout the recording by maintaining its distinct waveform. D-Amphetamine (1.0 mg/kg) was injected at t = 0 following the determination of baseline firing rate (defined as 100%) during quiet resting behavior. Data points are means + S.E.M. of firing rates derived from a counter output that cycled every 15-20 s. Absent error bar indicates S.E.M. < 15% of the mean.
_ 593% of the baseline rate, whereas inhibitions reached 11.5 + 6.4% of baseline. Amphetamine excited almost all (14 of 15) motor-responsive neurons, but only 3 of 9 nonmotor-related units. This difference in frequency of excitations was significant: ;(e(3) = 12.27, P < 0.01. Fig. 1 depicts examples of the excitatory and inhibitory responses to amphetamine. As shown in Fig. 2, histology revealed that amphetamine-excited, motor-responsive neurons were concentrated in the dorsolateral neostriatum. The only motor-related neuron inhibited by amphetamine showed an interesting behavior-dependent drug response. This neuron was inhibited during most amphetamine-induced behaviors, but activity associated with head movements was enhanced. In the latter respect, this neuron resembled other motor-related neurons: amphetamine typically enhanced activity related to locomotion, rearing, and head movements based on comparisons to firing rates obtained while rats displayed similar, discrete behaviors before amphetamine was injected. Thus,
367
i
ij ,.
-/...
iii
)
,, ,,~
,
'
Br~ma 0.2 mm
Bregma 0.7 mm
Bregma 1.2 mm
Fig. 2. Histologically verified sites of recorded single neurons. Squares and stars represent, respectively, motor- and nonmotor-responsive neurons. Closed and open figures represent, respectively, excitatory and inhibitory neuronal responses to amphetamine. Depicted coordinates of the coronal sections are distances anterior to bregma7. Note that motor-related neurons, which almost exclusively exhibit amphetamine-induced excitations, tend to concentrate in the dorsolateral neostriatum.
amphetamine typically enhanced neuronal activity associated with specific behaviors and increased performance of those behaviors. In agreement with previous studies of rats 4"]8 and monkeys 2, the majority (62%) of neostriatal neurons in our sample showed movement-related activity. Also supportive of previous w o r k 3"18 is our finding that this activity is largely excitatory, although movement-related inhibitions can be observed occasionally 4. Confirming our earlier results in freely moving rats 4"l°A1 and the preliminary results of others 12"~4, the amphetamine behavioral response was associated with both increases and decreases in neostriatal activity. Neurons showing motor-related activity were almost exclusively excited by amphetamine, whereas nonmotor-related neurons usually were inhibited by the drug. The tendency of motorrelated cells to concentrate in dorsolateral neostriaturn is consistent with lesioning studies indicating a role for this region in the control of limb movements 8.9. The present findings may help to clarify previous, apparently contrasting reports of neostriatal neuronal responses to amphetamine in freely moving rats. The greater prevalence and magnitude of excitatory
responses allow an explanation for the uniformly excitatory responses observed in multiple-unit recordings 5'15"16. Such recordings are likely to miss relatively infrequent inhibitory responses among high levels of excitation. Inhibitory responses, almost solely limited to nonmotor-related neurons, also are likely to be missed by selective recordings of motor-related cells 17'18. Though biased toward amphetamine-induced excitations, the selective recordings provided preliminary evidence that the excitations were not secondary to drug-induced behavioral changes 17']8. Drug effects secondary to behavior can be minimized to some extent by examining neuronal activity while the animals display similar, discrete behaviors before and after drug injection. Thus, a primary drug effect, rather than a neostriatal response to behavior, is suggested by our finding that motor-related neurons show amphetamine-induced excitations even when behavioral effects are controlled in the above manner. The possibility that these excitations are a primary drug effect is also supported by the in vitro finding of neostriatal neurons excited by amphetamine 13. Although this issue needs to be examined further, it appears that neuronal responses to am-
368 phetamine in the neostriatum are heterogeneous and that they are systematically related to the baseline motor-response characteristics of individual cells.
1 Ciancone, M.T. and Rebec, G.V., A simple device for the reliable production of varnish-insulated, high impedance tungsten microelectrodes, J. Neurosci. Methods, 27 (1988) 77-79. 2 Crutcher, M.D. and DeLong, M.R., Single cell studies of the primate putamen: I. Functional organization, Exp. Brain Res., 53 (1984) 233-243. 3 DeLong, M.R., Alexander, G.E., Mitchell, S.J. and Richardson, R.T., The contribution of basal ganglia to limb control, Prog. Brain Res., 63 (1986) 161-174. 4 Gardiner, T.W., Iverson, D.A. and Rebec, G.V., Heterogeneous responses of neostriatal neurons to amphetamine in freely moving rats, Brain Research, 463 (1988) 268-274. 5 Hansen, E.L. and McKenzie, G.M., Dexamphetamine increases striatal neuronal firing in freely moving rats, Neuropharmacology, 18 (1979) 547-552. 6 Haracz, J.L., Tschanz, J.T., Ciancone, M.T., Greenberg, J. and Rebec, G.V., Differential effects of haloperidol and clozapine on amphetamine-induced changes in behavior and neostriatal single-unit activity in freely moving rats, Soc. Neurosci. Abstr., 14 (1988) 664. 7 Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, Academic Press, Sydney, 1982. 8 Pisa, M., Motor somatotopy in the striatum of rat: manipulation, biting and gait, Behav. Brain Res., 27 (1988) 21-35. 9 Pisa, M. and Schranz, J.A., Dissociable roles of the rat's striatum conform to a somatotopic model, Behav. Neurosci., 102 (1988) 429-440. 10 Rebec, G.V., Electrophysiological pharmacology of amphetamine. In J. Marwah (Ed.), Neurobiology of Drug
This research was supported by USPHS G r a n t D A 02451 (G.V.R.). We also acknowledge the technical assistance of Dr. Mark Ciancone and Mr. Paul Langley. Abuse, Karger, Basel, 1987, pp. 1-33. 11 Rebec, G.V. and Gardiner, T.W., Regional effects of amphetamine in the neostriatum: single-unit responses in freely moving rats, Soc. Neurosci. Abstr., 11 (1985) 550. 12 Ryan, L.J., Young, S.J., Segal, D.S. and Groves, P.M., Antidromically identified striatonigral neurons are not excited by amphetamine in freely moving rats, Soc. Neurosci. Abstr., 12 (1986) 650. 13 Trulson, M.E. and Arastch, K., Effects of dopamine and amphetamine on mouse caudate neurons recorded in vitro, Eur. J. Pharmacol., 124 (1986) 161-165. 14 Trulson, M.E. and Jacobs, B.L., Effects of D-amphetamine on striatal unit activity and behavior in freely moving cats, Neuropharmacology, 18 (1979) 735-738. 15 Warenycia, M.W. and McKenzie, G.M., Immobilization of rats modifies the response of striatal neurons to dexamphetamine, Pharrnacol. Biochem. Behav., 21 (1984)53-59. 16 Warenycia, M.W. and McKenzie, G.M., Activation of striatal neurons by dexamphetamine is antagonized by degeneration of striatal dopaminergic terminals, J. Neural Transm., 70 (1987) 217-232. 17 West, M.O., Michael, A.J., Chapin, J.K. and Woodward, D.J., A strategy for separating behaviorally-related vs. drug-related changes in unit activity in freely moving rats, Soc. Neurosci. Abstr., 11 (1985) 687. 18 West, M.O., Michael, A.J., Knowles, S.E., Chapin, J.K. and Woodward, D.J., Striatal unit activity and the linkage between sensory and motor events. In J.S. Schneider and T.I. Lidsky (Eds.), Basal Ganglia and Behavior: Sensory Aspects of Motor Functioning, Hans Huber, Toronto, 1987, pp. 27-35.