Cardiovascular effects of septal, thalamic, hypothalamic and midbrain self-stimulation

Physiology & Behavior, Vol. 20, pp. 217-226. Pergamon Press and Brain Research Publ., 1978. Printed in the U.S.A.

Cardiovascular Effects of Septal, Thalamic, Hypothalamic and Midbi ain Self-Stimulation L. h.NGYh,N

Institute of Physiology, University Medical School, P~cs, Hungary (Received 12 October 1977)

A~IGYhtN, L. Cardiovasculareffects of septal, thalamic, hypothalamic and midbrain self-stimulation. PHYSIOL. BEHAV. 20(3) 217-226, 1978. - A positive correlation was found between the lever-pressing rate and the variability in the cardiovascular and respiratory effects elicited by septal, thalamic, hypothalamic and midbrain self-stimulation in cats. This correlation showed that all electrode placements which support self-stimulation are also capable of eliciting appropriate cardiovascular effects. The common characteristic of these effects was an increase in blood pressure, average respiratory and heart rates, and a decrease in pulse pressure during stimulation. Up to an unfavourably high level in the cardiovascular functions, self-stimulation at high rates was regularly assocaited with higher amplitude cardiovascular effects as compared to self-stimulation at low rates. Nonrewarding stimulation sites failed to evoke statistically significant changes in the cardiovascular responses. The instrumental alimentary behaviour was accompanied by an increase in blood pressure of about the same magnitude as self-stimulation at high rates. It was concluded that the cardiovascular effects are essential components of the behavioural pattern elicited by self-stimulation. Blood pressure

Heart rate

Instrumental alimentary behaviour

ALTHOUGH no one denies that both somatic and autonomic responses are components of all behavioural reactions, there are some disagreements among investigators concerning the importance of somatic-autonomic interactions in the control of specific types of behaviour. It has been demonstrated by several authors [12, 13, 14, 15, 16] that septal and hypothalamic self-stimulation elicit definite cardiovascular responses. Some other physiological correlates of self-stimulation were also reported [17]. At the same time, any visceral feedback was found to be unessential in self-stimulation [19]. However, considering the importance of the close integration of somatic and autonomic responses in the biological adaptation, a complete independence of self-stimulation behaviour from the evoked visceral effects would be disastrous. It suggests the need of further information about the r o l e ' o f autonomic effects of self-stimulation. Taking into consideration that a solution to the problem of experimentally separating somatic and autonomic response control is likely to prove elusive, the correlational observations are of special importance in determining the autonomic participation in selfstimulation behaviour. In our previous studies [1, 3, 5] a relationship was found between the lever-pressing behaviour and the autonomic effects of hypothalamic self-stimulation. However, this finding does not permit us any generalizations as to autonomic involvement in all self-stimulation behaviour, because the hypothalamus is certainly a center of importance to the regulation of autonomic nervous system function, and it is also highly involved in self-stimulation behaviour. Therefore, the aims of the present study were: ( 1 ) t o demonstrate correlative connections between the lever-pressing behaviour and the cardiovascular effects

Respiration

Self-stimulation

of septat, thalamic, hypothalamic and. midbrain self-stimulation; ( 2 ) t o compare the effect of rewarding stimulation with those of nonrewarding stimulation; and ( 3 ) t o compare the cardiovascular effects of self-stimulation with those accompanying a natural operant behaviour.

METHOD

Animals The experiments were carried out on twelve adult cats of both sexes weighing 2 - 4 kg at the time of surgery. Nine animals were trained to self-stimulate, and three cats were trained to press a lever for food. Surgery. Cats were anaesthetized with 40 mg/kg IV sodium pentobarbital. Bipolar electrodes were implanted in septal, thalamic, hypothalamic, midbrain and dorsal hippocampal regions by the conventional stereotaxic technique according to the coordinates of Jasper and Ajmone-Marsan [ 10] atlas. The electrodes consisted of 0.3 mm dia. stainless steel wires insulated except for 0.5 mm at the tip. The pole distance was 1 mm. At the same time a thermocouple was placed into the nasal orifice through the frontal sinus [4]. The wires were soldered to a miniture socket mounted on the skull with stainless steel screws and dental acrylic cement. Animals were permitted to convalesce for at least 1 week.

Behaviour Tests During the initial sessions the behavioural thresholds were determined for each electrode placement. 217

218

Self-Stimulation Test Cats were trained to self-stimulate by placing them repeatedly in contact with a lever. The 6 cm by 15 cm lever was fixed at a height of 10 cm above the floor of a 70 × 70 × 70 cm experimental cage. Self-stimulation training was not combined with pressing for food. The electrical stimulus consisted of monophasic square wave pulses with a pulse width of 0.3 msec and a frequency of 100 Hz. During the training procedure the optimum voltage was determined, i.e. the voltage at which the highest lever-pressing rate was obtained from each electrode placement. Two kinds of self-stimulation tests were instituted: (1) self-stimulation with fixed pulse train duration (0.3 sec), and (2) self-stimulation with self-regulation of pulse train duration, i.e. the electrical stimulation started when the animal depressed the lever, and the stimulation was turned off when the animal released the lever. A daily experimental session consisted of four 20 min self-stimulation periods each separated by a 20 min rest. During a 20 min testing period the animal was free to self-stimulate under constant experimental conditions. The animals were run under the condition of fixed pulse train duration on the first day, and with self-regulation of the pulse train duration on the second day. On the third experimental day another locus was tested. This procedure was repeated in the same order until stable patterns of self-stimulation were established. A locus was regarded to be nonrewarding if the animal failed to self-stimulate spontaneously after ten daily training sessions.

Instrumental Alimentary Behaviour In a cage of the same size as the cage for self-stimulation the animals were trained to press a lever for food. The lever, mounted on one of the walls of the cage, measured 6 cm by 15 cm, and was 10 cm above the floor. The cage was equipped with an automatic feeding device from which the animal received a small piece of meat every time it pressed on the lever. The response rate and the amount of meat consumed were measured during the daily 20 min experimental sessions.

Recordings and Data Analysis After the training procedure a second operation was made under sodium pentobarbital narcosis. A polyethylene catheter of 1.7 mm dia. and 1 m long was tied into one of the common carotid arteries. The catheter was filled with heparin. The other end of the catheter was brought out and fixed on the nape, so that the animal could not tear it out. Two days after surgery the blood pressure (BP), heart rate (HR), respiration rate (RR), and the hippocampal electrical activity were recorded continuously during the experimental sessions by means of a Hellige polyphysiograph. The results presented herein were obtained from the experimental sessions following the second operation in the same order as during the training procedure. For BP recording the catheter was connected to a Statham (P23Db) pressure transducer placed on the top of the experimental cage. ECG was recorded by means of safety-pin electrodes fastened into the skin of the chest. RR was recorded by the thermocouple implanted in the nasal orifice. The recordings of the hippocampal electrical activity served as indicator of epileptic seizure. The lever-pressing rate was measured by an electromechanic counter at five minute intervals. The

A NG Y AN duration of the individual stimulations was continuously recorded on the polyphysiograph. The effects of self-stimulation were compared to the prestimulation controls. Systolic and diastolic BP were analysed by measuring the ten highest pressures during the 20 min self-stimulation period. The HR was determined by counting the number of R waves in 10 sec intervals, and then converting these numbers to beats per minute by multiplying by 6. To reduce the masking effect of interstimulus intervals of varying duration the ten samples were taken from self-stimulation periods with interstimulus intervals shorter than 2 sec. However, this requirement often could not be fulfilled in cases of self-stimulation at low lever-pressing rates. The respiratory rate was similarly measured by counting the peaks of waves in the respiratory tracings. Means and SD were obtained for each self-stimulation period. The statistical evaluation of the data was based on correlated means [8].

Histology After the last experimental session, each cat was sacrificed by an overdose of sodium pentobarbital, its brain removed and fixed in 10% Formalin. The electrode tips were localized by a routine histological technique.

RESULTS

Description of R esponses The histologically verified location of the electrode tips are shown in Fig. 1. Electrode sites were classified on the basis of the maximum lever-pressing rate that could be maintained consistently across 20 rain trials: nonrewarding, low (~ 99), moderate ( 1 0 0 - 9 9 9 ) , and high (1000<). Seven out of 28 loci were non-rewarding, 9 supported low self-stimulation rates, 6 moderate, and 6 high rates. A l t h o u g h this study deals with the effects of stable patterns of self-stimulation, it is worth mentioning that at the beginning of training the animals often seemed to be confused by the stimulation, and exploratory, sniffing, licking-chewing movements appeared. In the course of training the confusion and the exploratory movements gradually disappeared, and the cats operated the lever by biting, mouthing, rubbing or pressing with the foreleg or with the chin. Besides the impressive similarities also some differences could be observed in the behavioural effects obtained from different brain regions. The animals were more active during midbrain and posterior hypothalamic self-stimulation than during septal and thalamic self-stimulation. Disturbing motor side effects (elevation of the foreleg, head turning, tilting of the body etc.) were elicited with stimulation of midbrain, posterior hypothalamic and two thalamic loci. Self-stimulation of septal, one thalamic and two hypothalamic placements regularly evoked seizure activity. Salivation, piloerection, urination often appeared during hypothalamic and midbrain self-stimulation. As expected the self-stimulation always elicited definite autonomic responses. The results are summarized in Table 1. Visually observed autonomic effects (pupillary changes, salivation, piloerection, urination etc.) were not treated statistically. It was a common finding that systolic and diastolic BP, average HR and RR increased during the short interstimulus interval repeated stimulus trains, and decreased during the sufficiently long interstimulus intervals.

CARDIOVASCULAR RESPONSES AND SELF-STIMULATION

219

Fr.2

Fr.8.0

Fr.11

Ft.3

Fr. 85

Fr. 12 _

Fr. 4

Fr. 90

Fr.13

Fr. 6

Fr. 9.5

••• moderate,l°w'n°nrewording ~ , ~ ~I highlever-pressirates ng Fr. 10.0

Fr.16

FIG. 1. Histologically verified localization of electrode tips in diagrams taken from the Jasper and Ajmone-Marsan stereotaxic atlas.

The pulse pressure decreased in the rising phase of BP responses, and increased in the descending phase. All statistical comparisons between mean values during prestimulation and self-stimulation periods were significant. However, remarkable differences were found in the magnitude of the responses elicited with self-stimulation of the different brain regions (Table 2, Fig. 2). BP, HR and RR changes of conspicuously higher amplitude were obtained from self-stimulation loci capable of inducing a high

lever-pressing rate, than from those supporting low frequency self-stimulation. Thus the data grouped on the basis of lever-pressing rate, leaving the structures out of consideration, show that self-stimulation at high rates elicited higher amplitude changes than self-stimulation at low rates (Table 3). These results show a correlation between the self-stimulation frequency and the change in the cardiovascular and respirator~J functions. For the group as a whole, the correlation coefficients between the lever-pressing rate (x)

220

ANGYAN TABLE l SUMMARY OF THE SELF-STIMULATION

Ln:b- BZa:I.n S e l f la%£on 9/9

~/9 ~/11

515

5/6

5/7

5/8

§li=mIAii,,,, s e e . m ~ -

/ m t HS/ / p e r n.tn/ / p e ~ n l n /

R

T

++

lo6/76

184

44

+++

106/76

184

44

H

-

127/116 127/116

234 234

x

H H

+++ +

125/lo3 130/113

H

+++

118/92 122/lo2

S

+

x

x

x

T

-

x

x

x

H

+++

155

3o

134/169

M

+

•

•

S T

+ +

H

lo9/93

117/129 1~4/151

lo3 115

94/95 lo9/11o

96 lo2

x

x

222 266

x •

146/145 142/142

loo loo

x x

182 163

• 19

lo3/112 13o/135

lo4 lo3

x

x

x

x

•

x

X

X

X

x

116/119 14o/129

117 119

165 173

157/141

113

x

164/146

lo3

215

lo5 111 128

135 128

x

x

x

++

98/81

121

+

lo3/84

123

$ T H

++ + +++

lo6/88 114/8o 121/89

152 148 16~

26 25 22

119/lo8 111/12o 133/149

M

-

x

x

X

S T

lo5/92 95/85 110/85 108/99

169 169 172 173

x

M

+ ++ +++ ++

112/117 110/112 120/142 142/14~

114 111 111 97

S T

-

84/69 86/71

~4 36

++ -

82/67

146 145 145 148

99/99 lo9/lo7 111/114 127/13o

94 117 112 121

H

•

90/70

x •

x

27

34

x

X

5

M

14o 132

x

X

M

+

lo7/9o lo6/92

79

218

16o

26 30 30 26

H

5/9

....

M

H

3119

Oaa1~ol

DATA

327

x x

• 135 139 177

315

Abbreviations: H ffi hypothalamus; M ffi midbrain; S = septum; T = thalamus; BP ffiblood pressure; HR = heart rate; R = respiratory rate; x = not measured. Self-stimulation: - = nonrewarding (manual stimulation); + = 1-99; ++ ffi 100"999 and +++ = 1000 or more responses per 20 rain.

and the increase in the cardiovascular and respiratory functions (y) are the following:

systolic BP diastolic BP heart rate respiratory rate

rxy 0.5433 0.7706 0.5635 0.2556

(N = 24) 7~ 0.01 0.00 l 0.01 not significant

Higher correlation was found between the lever-pressing rate (x) and the increase in the cardiovascular and respiratory responses (y) when the results were grouped according to the brain regions stimulated, and the mean values of

lever-pre.ing rate, BP, HR and RR effects o b t ~ e d for the septal, thalamic, hypothalamic and midbrain groups were correlated: (N = 4)

systolic BP diastolic BP heart rate respiratory rate

rxy 0.9945 0.9978 0.2365 0.9093

P 0.001 0.001 not significant 0.05

These results show that self-stimulation is associated with an appropriate increase in cardiovascular and respiratory functions. However, the evoked side effects m i g h t b e disturbing. Thus, midbrain stimulation producing high

CARDIOVASCULAR RESPONSES AND SELF-STIMULATION

221

TABLE 2 BLOOD PRESSURE EFFECTS OF HYPOTHALAMIC(H), MIDBRAIN (M), SEPTAL (S) AND THALAMIC(T) SELF-STIMULATION M

:eg:Lon

l:x~ls~JAlal&~a~ ~OD~Ol S71;tollo Dlutollo MOmm SD Mean SD

E£fecCs o f s e l f - s ~ l ~ L l & ¢ i 0 ~ Sys¢ol~o D*sstollo ~ : e a s / 2 o min Moan SD Heam SD Moan SD

H

8

113

14

92

14

155

28

131

27

898

673

H

3

106

~

86

12

154

14

127

14

719

638

$

4

lol

11

85

Zo

11~

20

95

14

72

85

T

4

lo5

8

8~

7

126

15

loo

1~

249

244

Blood pressure values are given in mm Hg. increase in BP, HR and RR supported self-stimulation only at low rate because the evoked motor side effects interfered with the lever-pressing behaviour. Since these data occurred in the group of low self-stimulation rates in Table 3, the mean increase in BP for this group is somewhat higher than that for the moderate self-stimulation rates. A stimulation evoking low amplitude cardiovascular effects never sustained self-stimulation at high rates. The septal stimulations evoked a mild increase in BP, HR and RR, and sustained self-stimulation only at low rates. Seemingly a stronger stimulation would have been more suitable for self-stimulation, but a slight increase in the stimulus intensity resulted in seizure activity.

A

The effects of self-stimulation with self-regulation of pulse train duration were substantially similar to those evoked by self-stimulation with fixed pulse train duration. The duration of the individual stimulations was very variable, especially at the beginning of the 20 rain trials, but the most frequent duration (about 70% of stimulations) was found to be shorter than 0.5 sec. However, in the case of one thalamic placement (Fig. 3b) extremely long ( 4 0 - 6 0 sec, or even longer) stimulations occurred. During such a long stimulation the BP never increased as high as during midbrain (Fig. 3a) or hypothalamic stimulations supporting self-stimulation at high rates, and also high amplitude fluctuations failed to appear in the BP recordings (Fig. 3b).

B

8.P

Stim. _ . . . . . . . .

C

D

mm Hg

1190

~L1hv~il-

.

.

.

.

.

.

.

.

.

.

,w--ImvP,,,mVl~.,-

"Pvlllllllvvv-',-'

|NC FIG. 2. Blood pressure (BP) and respiratory (Reap) effects of hypothalamic (B), septal (C), and thalmnic (D) self-stimulation in the one and the same animal. A: prestimulation control. Cat No. 5/7.

222

\N( ;Y AN TABLE3

INCREASE IN BLOOD PRESSURE DURING SELF-STIMULATION AT LOW (L), MODERATE (M) AND HIGH (H) RATES, AND DURING MANUAL STIMULATION OF NO~IREWARDING (NR) LOCI N

S~Imula~Ion

STIr~o.l.io 3? /,m ag/

Die'tolleBP /ram Hg/

Xean

SD

p

Mean

SD

p

~O

25

.02

23

17

. ol

L

7

M

6

27

19

.o2

21

15

.o2

H

6

41

15

.ool

44

ii

.ool

NR

5

i

15

no

4

9

ns

The cat was generally motionless, resembling an arrest o~ crouching reaction, however, stronger stimulation was required to evoke a tonic immobility from the same locus in an indifferent situation than that supporting self-stimulation. The duration of the individual stimulations seemed to be related to the cardiovascular effects; the animal released the lever whenever the evoked effects surpassed an unfavourable level (Fig. 3a). So, a stimulation evoking high increase in the cardiovascular functions supported self-stimulation at shorter pulse train duration and higher lever-pressing rate than that evoking moderate cardiovascular effects. If a stimulation failed to evoke cardiovascular changes of sufficiently high amplitude, then the cat left the lever after several presses on it. In accordance with our earlier results, the cardiovascular functions returned near the control levels during extinction, in spite of that the animal pressed the lever several times.

Effects of Nonrewarding Stimulation Resp. ~ L.Hip

I

L~. --'~

........

~ .............

Slim.

~

T ,,,i, 'L'.' ..... /7. ......" " ~ : ~ - ~

..,._.-~:~..

]

For the group as a whole, no significant cardiovascular and respiratory effects were obtained with manual stimulation of the five nonrewarding loci (Table 3). The stimulus voltage was gradually increased until strong motor effects (turning, circling, escape, etc.) appeared. Self-stimulation was mimicked manually, and also sustaining (5 see) stimulations were applied. Stimulations at threshold and medium intensities evoked only small alterations in BP, average HR and RR. In two cases a slight fall in BP (maximum 20 mm Hg) was obtained. Strong stimulation evoked an increase in cardiovascular functions, but in all but one case this increase was smaller than that elicited with self-stimulation at high rates. Stimulation of a midbrain locus elicited an increase in the cardiovascular functions of about 130% of control, however, this stimulation evoked strong motor side effects, and also long-lasting disturbances (repeated extrasystoles) appeared in the heart activity after several stimulations (Fig. 4).

B2

Comparison with Instrumental A limentary Behaviour

B3 1-190m m 1-19 . . . . . . .

-

.

.

.

.

.

.

.

.

.

.

,,

.

i i i

.

.

.

.

, . - ~ .......................................

.

•. . . . . . . . . .

~.... ~.......~ I ~ " z1~

.

.

.

.

.

.

.

.

.

.

l~e

FIG. 3. Effects of a midbrain (A) and a thalamic (B) sdf-stimulation with self-regulation of pulse train duration. The electrode placements in the midbrain (a) and in the thalamus Co) are shown in the diagrams. B, shows the onset, B2 the middle, and B3 the termination of a continuous stimulation lasting 60 sec. Abbreviations: BP = blood pressure, Resp = respiration, L. Hip = left dorsal hippocampus. Cat No. 9/9.

The finding that self-stimulation at high rates occurred regularly with a mean increase in BP of about 40 mm Hg, raised the question as to what changes occur in BP during a natural operant behaviour. To answer this question 3 cats were trained to press a lever for food. The cardiovascular responses were recorded continuously during the daily 20 min trials. The mean lever-pressing rate was 96 (SD 52), and the mean quantity of meat consumed was 190 (SD 110)g. The mean increase in systolic BP was 49 (SD 13) mm Hg, and that in diastolic BP was 45 (SD 12) mm Hg. Thus. somewhat higher increase in BP was obtained during lever-pressing for food than during self-stimulation at high rates (Fig. 5). It is noteworthy that the mean increase in systolic BP was higher than that in diastolic BP during instrumental alimentary behaviour, while the mean increase in diastolic BP surpassed the mean increase in systolic BP during self-stimulation. Average HR increased to 1 t 7% (SD 3) of control values. The mean increase in BP was 16 mm Hg during extinction of the alimentary response. The BP response to a natural consummatory behaviour was also recorded in a self-stimulating cat. A dish of meat was placed in the experimental chamber after a 20 min self-stimulation period, and the cat was left free to eat. BP

CARDIOVASCULAR RESPONSES AND SELF-STIMULATION

A

223

B

Stim.--n

~

n__

C

10 sec

I

I

f"'L FIG. 4. Respiratory (Resp) and blood pressure (BP) effects evoked by manual stimulation of a nonrewarding midbrain placement. The duration of stimulation was gradually increased from A to C. C shows repeated extrasystoles following the stimulation. Cat No. 5/9. increased to about the same level during eating as during self-stimulation at high rates (Fig. 6). DISCUSSION

Notwithstanding that the brain regions under study were sampled too sparsely, the results show that self-stimulation is always associated with definite cardiovascular and respiratory effects. The c o m m o n characteristic of these effects is an increase in systolic and diastolic BP, and average HR and RR. Similar results were obtained from hypothalamic self-stimulation in dogs [16]. In our earlier experiments [1,5] a slight fall in BP was evoked by self-stimulation in one out of 21 cats, and a biphasic BP response in two other cases. In the present study such BP effects failed to occur. It was reported that septal self-stimulation usually produces a deceleration o f HR [I 2,15]. Later, Malmo [13] found in rats that stimulation of the lateral septal area produced slowing of HR, and the medial placements produce an initial acceleration followed by deceleration. The septal electrodes were placed close to the midline in our cats, thus the present findings are in substantial agreement with Malmo's results despite the species difference. Even if a decrease o f average HR was obtained during self-stimulation, the careful analysis of the ECG tracings showed that the pronounced deceleration was preceded by an initial acceleration of HR after each stimulus train. On the basis of the consistent appearance of marked

cardiovascular and respiratory effects during self-stimulation these effects can be regarded as components indispensable to self-stimulation behaviour. However, a widespread assumption in the literature is that the cardiovascular effects are not essential and therefore unimportant in the maintenance of self-stimulation. This view is strongly supported by the following evidences. First, Perez-Cruet et al. [16] showed that self-stimulation was not affected b y blocking the increase in BP with injection of dibenzyline. Second, Ward and Hester [19] demonstrated in cats that self-stimulation was unimpaired by surgical sympathectomy, vagotomy, and sectioning of the pelvic splanchnic nerves. However, considering that the autonomic nervous system can react as an integrated whole, and also specific subdivisions can independently come into action [ l l ] , these results do not exclude the autonomic involvement in self-stimulation behaviour. Under the effect of dibenzyline the rise in BP was blocked but the HR increased showing the autonomic activation, on the one hand, and, it is well known that a surgical separation of the brain and the peripheral autonomic nervous system is always incomplete, on the other. It should be noted that self-stimulation was found to be suppressed by i m m u n o s y m p a t h e c t o m y [18], and other investigators found changes in self-stimulation behaviour also after vagotomy [2, 3, 6]. On the basis of the relevant literature it is not surprising to find that both the absolute and the relative magnitude of the cardiovascular and respiratory effects of self-stimulation

224

ANG Y AN

mm Hg

systolic B P diastolic BP

60-

50fJ fJ

t,0-

f,o fJ p'j JJ fJ fJ

30-

zf J fJ

fJ fJ

20-

f, fal f.

z

10-

f# fJ f# fJ f#

fJ []

NR N 5

SS 6

AB 3

FIG. 5. Mean increase in blood pressure during manual stimulation of nonrewarding loci (NR), during self-stimulation at high rates (SS), and during instrumental alimentary behaviour (AB). varied markedly with the location of the electrode in the brain. Similarly, a variety of lever-pressing behaviour could be observed during self-stimulation of the brain regions under study, in general agreement with the findings of Wilkinson and Peele [20]. What is new in this study is that a systematic relationship is revealed between the lever-pressing rate and the variability in the cardiovascular and respiratory effects. This relationship serves to emphasize that those electrode placements which support self-stimulation, should be also capable of evoking appropriate cardiovascular effects. According to the positive correlation, up to an unfavourable level of cardiovascular functions, self-stimulation at higher rates is associated with higher amplitude cardiovascular effects, as opposed to self-stimulation at low rates. Two points seem to be important here. First, the rate as a measure of reward is widely discussed in the literature. However,, within a given electrode localization rate correlates well with the reward value [9], on the one hand, and substantially the same relationship was found between the cardiovascular effects and the lever-pressing behaviour during self-stimulation with self-regulation of pulse train duration, than during self-stimulation with fixed pulse train duration, on the other. Second, the central origin of the

cardiovascular responses is shown by the fact that they return to near the control levels during extinction, when the cat presses the lever without receiving electrical stimulation. Self-stimulation at high rates elicited a mean increase in BP of about 40 mm Hg. In contrast with this the nonrewarding stimulations failed to evoke statistically significant BP effects. Taking into consideration also the finding that the alimentary behaviour is accompanied by an increase in BP of about 50 mm Hg, it would be a plausible assumption that the animal self-stimulates to increase its own BP. However, such a causal importance of BP changes was refuted by the observation that the blockade of the increase in BP does not interrupt self-stimulation [ 16 ]. The arterial blood pressure is compounded by many cardiovascular variables, thus it would be simple-minded to regard BP as a separate entity, especially in a freely behaving animal. It seems to be more reasonable to take into consideration all components of self-stimulation behaviour as an integrated whole, rather than to regard separately either of them as of causal importance. On the basis of the somatic and autonomic manifestations it can be suggested that self-stimulation activates some built-in patterns significant to natural consummatory behaviours. The following evidences seem to support this suggestion. ( t ) Despite the variable side effects elicited with self-stimulation of different brain loci some elements of a consummatory behavioural pattern (such as licking-chewing movements, salivation, etc.) always could be recognized. (2)Non-rewarding stimulations failed to evoke a behavioral pattern resembling to consummatory action. (3) Both the pattern and the magnitude of cardiovascular effects obtained during instrumental alimentary behaviour were similar to those evoked by self-stimulation at high rates. On the basis of this suggestion it is clear that animals seemed to be confused by the appropriate stimulation at the beginning of self-stimulation training, because the stimulation evoked a consummatory pattern in a situation providing no consummatory goal object. Of related interest is the finding on rats that the bar press rate was significantly higher when goal objects were present in the chamber [7]. Previous reports [ 1, 2, 3, 6] suggested the importance of a feedback mechanism in the timing of lever-pressing behaviour. The present results support this suggestion showing that the animal stopped self-stimulating whenever the magnitude of evoked cardiovascular effects surpassed an optimum level. This effect could be observed both during self-stimulation with fixed pulse train duration and with self-regulation of pulse train duration. At a thalamic placement long-lasting stimulations occurred during selfstimulation with self-regulation of pulse train duration. Considering that the cardiovascular effects were kept constant at about the optimum level during stimulation, this finding tends to support rather than deny the role of a peripheral feedback mechanism. To summarize, it may be concluded that the cardiovascular effects are essential for self-stimulation behaviour as components of the evoked behavioural pattern which is compounded of variable somatic and autonomic elements. Furthermore, they play a role in the timing of lever-pressing behaviour by means of a peripheral feedback mechanism. ACKNOWLEDGEMENT

This work was supported by the Scientific Research Council, Ministry of Health, Hungary, No. 3 - 3 5 - 0 3 0 3 - 0 1 - 0 / A .

C A R D I O V A S C U L A R RESPONSES AND SELF-STIMULATION

225

A T

B.P. ~ ,

B

C

mm

= ,,,..~; ~ . . - : : - : ~ ' :

~,,

~

t

Hg

200 150

'.......... - "-~ ~...~. , 1 0 0

,10 see FIG. 6. Blood pressure (BP) responses recorded during self-stimulation (Stim) at high rates (A), and during eating small pieces of meat (B). C: prestimulation control. Cat No. 3/11.

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