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Modulation of passive avoidance behaviour by cholecystokinin octapeptides in rats
Neuropeptides 1: 301-307, 1981
MODULATION OCTAPEPTIDES Mgtyes Department Chemistry, Hungary
0~
Fekete,
PASSIVE IN RATS Tibor
AVOIDANCE Kgdhr,
of Pathophysiology University Medical (reprint requests to
BEHAVIOUR
Botond
PenkeX
BY C~~OLECYSTOKININ and
and ‘Department School, Szeged, GT)
Gyula
Telegdy
of Medical P.O.BOX 531,
ABSTRACT The effects of two different doses of cholecystokinin octapeptide sulphate ester and its unsulphated form on the passive avoidance behaviour were studied following intraperitoneal administration to rats. Administered immediately after the learning trial in a dose of 400 nmole/kg, both peptides resulted in significantly increased passive avoidance latencies as compared to the control, There were no effects on the latency of passive avoidance behaviour when the animals were treated 1 h before the learning trial. When the cholecystokinin octapeptides were given 23 h after the learning trial, the latency tended to be increased, but this difference was not statistically Significant. INTRODUCTION The presence of cholecystokinin (CCK) in the brain of different species (for reviews, see (1,2)) and in the cerebrospinal fluid of man (3) suggests the important role of this neuropeptide in brain functions. In several studies, CCK has been shown to depress the food intake in rats, monkeys and many other species (for reviews, see (4,5) ). However, conflicting data are also to be found in the literature (6,7,8). Zetler (9,lO) demonstrated antinociceptive effects, palpebral ptosis, sedation and a prolonged hexobarbital sleeping time following CCK octapeptide treatment. In our earlier experiments it was shown that intracerebroventricular administration of cholecystokinin octapeptide sulphate ester (Ccl<-8-SE) modified the activity of the monoaminergic system in the brain (11‘12, 13, 14), whereas unsulphated cholecystokinin octapeptide (CCK-8-NS) was practically ineffective (15). In our behavioural experiments it was demonstrated that in CCK-8-SE and Ccl<-~-NS treated animals the acquisition of conditioned feeding behaviour was considerably impaired as compared to the control,
301
When the animals had learned the conditioned reflex,the hunger motivation was no longer needed, and therefore CCK-8-SE and CCK-8-NS were unable to modify the maintenance of this conditioned reflex (16). In the present paper the effects of CCK-8-NS and CCK-8-SE on the passive avoidance behaviour of rats have been studied. MATERIALS 1.
AND METHODS
Animals
Experiments were performed on male CFY rats weighing 150-180 g, housed 5-6 per cage with free access to food and tap water. The animals were kept on an artificial light schedule (12 h light, 12 h dark), the light period starting at Experiments were carried out daily between 6 a.m. and 6 a.m. noon. 2.
Apparatus
The platform (40 x 30 3.
experimental apparatus (30 x 7 cm) attached x 30 cm) with a grid
consisted to a large floor.
of an illuminated dark compartment
Procedure
One-trial learning step-through passive avoidance behaviour was measured according to Ader and de Wied (17). Rats were placed on the platform and allowed to enter the dark Since rats prefer dark to light, they normally compartment. entered within 15 s. Two additional trials were given on the After the second one, unavoidable electric following day. footshocks (3.0 mA, 2 s) were delivered through the grid floor After this single learning trial, of the dark compartment. the rats were immediately removed from the apparatus. Passive avoidance behaviour was tested 24 h after the learning trial: the rats were placed on the platform and the latency to enter the dark compartment was measured up to a maximum of 300 S. 4.
Treatment
CCK-8-NS and Ccl<-8-SE were synthetized by Penke et al. (18). Peptides were dissolved in physiological saline solution and given intraperitoneally in doses of 4 nmole/kg (4.6 and 5.0 ug/kg) and 400 nmole/kg (460 and 500 ug/kg) in a volume of 1.0 ml/kg. Control animals received physiological saline solution in a volume of 1.0 ml/kg. Passive avoidance behaviour I: animals were treated 1 h 25 h before the next test. before the shock, i.e. Passive avoidance behaviour II: animals were treated immediately after the tick, i.e. 24 h before the next test. Passive avoidance behaviour III: animals were treated 23 h after the shock, i.e. 1 h before the next test. 5.
Statistical
evaluation
Statistical analysis analysis of variance.
of
the
302
results
was
performed
by
RESULTS When the animals were treated with peptides 1 h before there were no differences in the latencies of pa.sshock, avoidance behaviour (Fig. 1). Administration of CCK-8-NS and CCK-8-SE in a dose of 400 nmole/kg immediately after the learning trial resulted in sig0.05) increased passive avoidance latencies as nificantly (p compared to the control (Fig. 2). not statistically significant There were only slight, increases in the latency of passive avoidance behaviour when the animals were treated 23 h after the shock (Fig. 3).
the sive
PASSIVE
AVOIDANCE I
BEHAVIOUR
0 CONTROL m CCK-8-NS, m CCK-8-NS,
4 NMOLE/KG. 400
q CCK-B-SE, aCCK-&SE,
Fig.
1.
NMOLEIKG.
Ii? IF!
4
NMOLEIKG.
IF!
400
NMOLEIKG,
Ii?
Effects of two different and CCK-8-6~ on latency behaviour. Animals were the test. The number of the bottom of the columns; indicate standard error
303
doses of CCK-8-NS of passive avoidance treated 25 h before animals is shown at vertical lines of mean.
PASSIVE AVOIDANCE II
BEHAVlOljR 2. Effects of two different doses of Ccl<-~-NS and CCK-8-SE on latency of passive avoidance behaviour Animals were treated 24 h before the test.
Fig.
0
= p(
0.05
versus
control
0 CONTROL a CCK-B-NS. BCCK-8-NS. 0 CCK-B-SE, @ CCK-8-X.
4 NMOLEIKG, 400
NMOLEIKG,
4 NMOLEIKG. 400
NMOLEIKG.
If? IF! It? if?
PASSIVE AVOIDANCE III
J 3. Effects of two Fig. different doses of CCK-8-NS and CCK-8-SE on latency of passive avoidance behaviour. Animals were treated 1 h before the test.
BEHAVIOUR
T
1 !! 0 0
0 0 0 0 0 0 0 0 0
q CONTROL
4 NMOLEIKG.
B CCK-8-NS.
Ii?
@CCK-8-NS.
400
NMOLEIhG.
IF!
•I CCK-&SE,
4
NMOLEIKG.
IF!
NMOLE/KG,
IF!
q lCCK-a-SE.
304
0 0 0 0 0 0 0 0 0 0
400
DISCUSSION Large amounts of CCK have been shown to be present in the brain of different species (19,20). The presence of specific cholecystokinin receptors in the brain has also been demonstrated (21,22). Goltermann et al. (23) revealed a substantial de novo synthesis of CCK in subcortical regions of brain CCI<-conthe brain. Malesci et al, (24) d emonstrated The exact functional role of CCK in the verting enzymes. central nervous system is not fully understood. In the present study neither CCK-8-NS nor CCK-8-SE had any effect on the learning of a passive avoidance task. This is in contrast with the results of our earlier study, which demonstrated that hunger-motivated learning is impaired by CCI< octapeptides (16). CCK-8-NS and CCK-8-SE increased the latency of passive avoidance behaviour of rats, showing that CCI< interferes with the memory, facilitating it. CCK octapeptides given 23 h following electric shock tended to inwhich might suggest that CCK octapeptides crease the latency, facilitate the retrieval of memory processes and also of fear-motivated behaviour. The possibility should be considered that the currently observed action of CCK octapeptides on the latency of passive avoidance behaviour could be a peripheral influence of these peptides on gall-bladder contraction, increased pancreatic secretion, etc., causing discomfort to the animals, which might affect the motor activity. However, this possibility can be ruled out, since the cholecystokinetic effect of CCK-8-SE, analyzed either in vivo (25) or in vitro (26), is much stronger than that of its unsulphated form; neither Ccl<-~-SE nor CCK-8-NS influence the open-field activity of rats (27). ACI
authors
wish
to
thank
Mrs
I<.
Boda
for
statistical
REFERENCES 1.
Loonen ,A. J. and Soudi jn ,W. (1979). function : central neuroregulators J. Physiol. (Paris) 75, 831-850.
2.
Hokfelt ,T., Johansson ,O. , and Schultzberg ,M. (1980). 284, 515-521.
3.
Rehfeld ,J. F. and Kruse-Larsen ,C. (1978). cholecystokinin in human cerebrospinal chemical determination of concentrations heterogeneity. Brain Res. 155, 19-26.
4.
Mueller,K. cystokinin Biobehav.
and Hsiao,S. as a short-term Rev. 2, 79-87.
Ljungdahl Peptidergic
Peptides and gut
,A.
,
with dual hormones.
Lundberg neruones.
,3.M. Nature
Gastrin and fluid. Immunoand molecular
(1978). Current status of cholesatiety hormone. Neurosci.
305
5.
Della-Fera,A.A. and Baile,C.A. injected in CSF decreases meal in sheep. Peptides 1, 51-54.
6.
Sturdevant,R.A.L. and Goetz,H. both stimulates and inhibits Nature 261, 713-715.
7.
Greenway satiety.
8.
Snapir ,N. and Glick,Z. size in the domestic
9.
Zetler,G. on rearing European
,F. L. Life
and Sci.
(1980). CCK-octapeptide size and daily food
(1976) Cholecystokinin human food intake.
(1977).Cholecystokinin ,G.A. 269-272.
Bray 21,
intake
(1978).Cholecystokinin fowl. PhysioI. Behav.
and
21,
(1980).Effects of cholecystokinin-like activity and hexobarbital-induced J. Pharmacol. 66, 137-139. and ptosis octapeptide
and meal 1051-1052. peptides sleep.
10.
(1980).Analgesia Zetler ,G. rulein and cholecystokinin pharmacology 19, 415-422.
11.
Telegdy,G., Fekete ,M. and Varszegi ,M. (1979). Effects of peptide hormones on the neurotransmitter metabolism of the central nervous system. In: Laszl6,F.A. (ed.) Recent Results in Peptide Hormone and Androgenic Steroid ReAkademiai I
12.
,M., Penke ,B, , Kovacs ,I<. and Telegdy, Fekete ,M. , Varszegi G. (1980).Effects of intracerebroventricular administration of cholecystokinin octapeptide sulfate ester on norepinephrine and serotonin contents of difdopamine, ferent brain structures in rats. Neuroendocrinology Letters 2, 67-72.
13.
Varszegi ,M. , Kader ,T. , Penke ,B,, , I
14.
Fekete,M., KBdar,T., Penke,B., Kovacs,K. and (1981).Influence of cholecystokinin octapeptide ester on brain monoamine metabolism in rats, Neural Transmission,in press.
15.
Fekete,M., KBdar,T., Varszegi,M., Bokor,M,, (1981). The effects and Kovacs ,K. Penke ,B. and unsulfated cholecystokinin octapeptide amine contents in rats. In: Proc. of the Union of Physiological Sciences. Akademiai in press. pest,
306
caused by (Ccl<-8).
caeNeuro-
Telegdy,G. sulfate Journal of
Telegdy,G., of sulfated on brain monoInternational Kiado, Buda-
16.
and Telegdy,G. (1981). Fekete ,M. , Balazs ,M. , Penke ,B. Influence of cholecystokinin octapeptide sulfate ester and unsulfated cholecystokinin octapeptide on conditioned feeding behaviour in rats. Physiol.Behav. in press.
17.
Ader
and de Wied,D. (1972). and passive avoidance 46-48. ,R.
active 29,
Effects learning.
of vasopressin Psychon.Sci.
on
18.
, Kovacs ,I<. , Kovacs ,L. and Balaspiri, Penke ,B. , Zarandy,M, L. (1979).Synthesis of cholecystokinin octapeptide sulfate ester. In: Kupriszewsky,G. (ed. ) Peptides 1978. Wroclaw University Publ.Co., Wroclaw, p. 581-584.
19.
(1978). Rehfeld ,3. F. and adenohypophysis.
20.
Vanderhaeghen,J.J., (1980).Immunohistochemical kininand gastrin-like physis of the rat. 1190-1194.
21.
Saito,A., (1980). terization
22.
Hays ,S.E. Paul ,S.M. site for 1, 53-62.
23.
Goltermann ,N.S., Rehfeld ,J. F. and Concentration and in vivo synthesis in subcortical regions of the rat 35, 479-483.
24.
Malesci,A., Straus,E. and Yalow,R.S. kinin-converting enzymes in brain. U.S.A. 77, 597-599.
25.
Johnson, L. R. , Stening ,G. F. Effect of sulfation on the caerulein. Gastroenterology
Localization Nature 271,
of gastrins 771-773.
to
neuro-
de Mey,J. and Gilles ,C. localization of cholecystopeptides in the brain and hypoProc.Nat. Acad.Sci. U.S.A. 77, Lotstre,F.,
Goldfine,I.D. Sankaran.H., Cholecystokinin receptors in and distribution. Science
and Williams,J.A. the brain: charac208, 1155-1156.
, Beinfeld,M.C.,
Jensen,R.T., Goodwin,F.K. (1980) Demonstration of a putative receptor cholecystokinin in rat brain. Neuropeptides
and
Petersen ,H.R. (1980). of cholecystokinin brain. J.Neurochem.
(1980).CholecystoProc.Nat.Acad.Sci.
and Grossman gastrointestinal 58, 208-216.
,M. I.
(1970). actions
of
26.
Chowdhury ,3. R. , Berkowitz ,J.M. , Praissman ,M. and Fara, J.W. (1976),Effect of sulfated and non-sulfated gastrin and octapeptide-cholecystokinin on cat gall bladder in vitro. Experientia 32, 1173-1175.
27.
Fekete,M., Bokor,M., Penke,B., ot cholecystokinin octapeptide unsulphated cholecystokinin avoidance behaviour in rats. in press.
Accepted 20th February, 1981 307
Telegdy,G. sulphate octapeptide Behavioural
(198l).Effects ester and on active Brain Research,
MODULATION OCTAPEPTIDES Mgtyes Department Chemistry, Hungary
0~
Fekete,
PASSIVE IN RATS Tibor
AVOIDANCE Kgdhr,
of Pathophysiology University Medical (reprint requests to
BEHAVIOUR
Botond
PenkeX
BY C~~OLECYSTOKININ and
and ‘Department School, Szeged, GT)
Gyula
Telegdy
of Medical P.O.BOX 531,
ABSTRACT The effects of two different doses of cholecystokinin octapeptide sulphate ester and its unsulphated form on the passive avoidance behaviour were studied following intraperitoneal administration to rats. Administered immediately after the learning trial in a dose of 400 nmole/kg, both peptides resulted in significantly increased passive avoidance latencies as compared to the control, There were no effects on the latency of passive avoidance behaviour when the animals were treated 1 h before the learning trial. When the cholecystokinin octapeptides were given 23 h after the learning trial, the latency tended to be increased, but this difference was not statistically Significant. INTRODUCTION The presence of cholecystokinin (CCK) in the brain of different species (for reviews, see (1,2)) and in the cerebrospinal fluid of man (3) suggests the important role of this neuropeptide in brain functions. In several studies, CCK has been shown to depress the food intake in rats, monkeys and many other species (for reviews, see (4,5) ). However, conflicting data are also to be found in the literature (6,7,8). Zetler (9,lO) demonstrated antinociceptive effects, palpebral ptosis, sedation and a prolonged hexobarbital sleeping time following CCK octapeptide treatment. In our earlier experiments it was shown that intracerebroventricular administration of cholecystokinin octapeptide sulphate ester (Ccl<-8-SE) modified the activity of the monoaminergic system in the brain (11‘12, 13, 14), whereas unsulphated cholecystokinin octapeptide (CCK-8-NS) was practically ineffective (15). In our behavioural experiments it was demonstrated that in CCK-8-SE and Ccl<-~-NS treated animals the acquisition of conditioned feeding behaviour was considerably impaired as compared to the control,
301
When the animals had learned the conditioned reflex,the hunger motivation was no longer needed, and therefore CCK-8-SE and CCK-8-NS were unable to modify the maintenance of this conditioned reflex (16). In the present paper the effects of CCK-8-NS and CCK-8-SE on the passive avoidance behaviour of rats have been studied. MATERIALS 1.
AND METHODS
Animals
Experiments were performed on male CFY rats weighing 150-180 g, housed 5-6 per cage with free access to food and tap water. The animals were kept on an artificial light schedule (12 h light, 12 h dark), the light period starting at Experiments were carried out daily between 6 a.m. and 6 a.m. noon. 2.
Apparatus
The platform (40 x 30 3.
experimental apparatus (30 x 7 cm) attached x 30 cm) with a grid
consisted to a large floor.
of an illuminated dark compartment
Procedure
One-trial learning step-through passive avoidance behaviour was measured according to Ader and de Wied (17). Rats were placed on the platform and allowed to enter the dark Since rats prefer dark to light, they normally compartment. entered within 15 s. Two additional trials were given on the After the second one, unavoidable electric following day. footshocks (3.0 mA, 2 s) were delivered through the grid floor After this single learning trial, of the dark compartment. the rats were immediately removed from the apparatus. Passive avoidance behaviour was tested 24 h after the learning trial: the rats were placed on the platform and the latency to enter the dark compartment was measured up to a maximum of 300 S. 4.
Treatment
CCK-8-NS and Ccl<-8-SE were synthetized by Penke et al. (18). Peptides were dissolved in physiological saline solution and given intraperitoneally in doses of 4 nmole/kg (4.6 and 5.0 ug/kg) and 400 nmole/kg (460 and 500 ug/kg) in a volume of 1.0 ml/kg. Control animals received physiological saline solution in a volume of 1.0 ml/kg. Passive avoidance behaviour I: animals were treated 1 h 25 h before the next test. before the shock, i.e. Passive avoidance behaviour II: animals were treated immediately after the tick, i.e. 24 h before the next test. Passive avoidance behaviour III: animals were treated 23 h after the shock, i.e. 1 h before the next test. 5.
Statistical
evaluation
Statistical analysis analysis of variance.
of
the
302
results
was
performed
by
RESULTS When the animals were treated with peptides 1 h before there were no differences in the latencies of pa.sshock, avoidance behaviour (Fig. 1). Administration of CCK-8-NS and CCK-8-SE in a dose of 400 nmole/kg immediately after the learning trial resulted in sig0.05) increased passive avoidance latencies as nificantly (p compared to the control (Fig. 2). not statistically significant There were only slight, increases in the latency of passive avoidance behaviour when the animals were treated 23 h after the shock (Fig. 3).
the sive
PASSIVE
AVOIDANCE I
BEHAVIOUR
0 CONTROL m CCK-8-NS, m CCK-8-NS,
4 NMOLE/KG. 400
q CCK-B-SE, aCCK-&SE,
Fig.
1.
NMOLEIKG.
Ii? IF!
4
NMOLEIKG.
IF!
400
NMOLEIKG,
Ii?
Effects of two different and CCK-8-6~ on latency behaviour. Animals were the test. The number of the bottom of the columns; indicate standard error
303
doses of CCK-8-NS of passive avoidance treated 25 h before animals is shown at vertical lines of mean.
PASSIVE AVOIDANCE II
BEHAVlOljR 2. Effects of two different doses of Ccl<-~-NS and CCK-8-SE on latency of passive avoidance behaviour Animals were treated 24 h before the test.
Fig.
0
= p(
0.05
versus
control
0 CONTROL a CCK-B-NS. BCCK-8-NS. 0 CCK-B-SE, @ CCK-8-X.
4 NMOLEIKG, 400
NMOLEIKG,
4 NMOLEIKG. 400
NMOLEIKG.
If? IF! It? if?
PASSIVE AVOIDANCE III
J 3. Effects of two Fig. different doses of CCK-8-NS and CCK-8-SE on latency of passive avoidance behaviour. Animals were treated 1 h before the test.
BEHAVIOUR
T
1 !! 0 0
0 0 0 0 0 0 0 0 0
q CONTROL
4 NMOLEIKG.
B CCK-8-NS.
Ii?
@CCK-8-NS.
400
NMOLEIhG.
IF!
•I CCK-&SE,
4
NMOLEIKG.
IF!
NMOLE/KG,
IF!
q lCCK-a-SE.
304
0 0 0 0 0 0 0 0 0 0
400
DISCUSSION Large amounts of CCK have been shown to be present in the brain of different species (19,20). The presence of specific cholecystokinin receptors in the brain has also been demonstrated (21,22). Goltermann et al. (23) revealed a substantial de novo synthesis of CCK in subcortical regions of brain CCI<-conthe brain. Malesci et al, (24) d emonstrated The exact functional role of CCK in the verting enzymes. central nervous system is not fully understood. In the present study neither CCK-8-NS nor CCK-8-SE had any effect on the learning of a passive avoidance task. This is in contrast with the results of our earlier study, which demonstrated that hunger-motivated learning is impaired by CCI< octapeptides (16). CCK-8-NS and CCK-8-SE increased the latency of passive avoidance behaviour of rats, showing that CCI< interferes with the memory, facilitating it. CCK octapeptides given 23 h following electric shock tended to inwhich might suggest that CCK octapeptides crease the latency, facilitate the retrieval of memory processes and also of fear-motivated behaviour. The possibility should be considered that the currently observed action of CCK octapeptides on the latency of passive avoidance behaviour could be a peripheral influence of these peptides on gall-bladder contraction, increased pancreatic secretion, etc., causing discomfort to the animals, which might affect the motor activity. However, this possibility can be ruled out, since the cholecystokinetic effect of CCK-8-SE, analyzed either in vivo (25) or in vitro (26), is much stronger than that of its unsulphated form; neither Ccl<-~-SE nor CCK-8-NS influence the open-field activity of rats (27). ACI
authors
wish
to
thank
Mrs
I<.
Boda
for
statistical
REFERENCES 1.
Loonen ,A. J. and Soudi jn ,W. (1979). function : central neuroregulators J. Physiol. (Paris) 75, 831-850.
2.
Hokfelt ,T., Johansson ,O. , and Schultzberg ,M. (1980). 284, 515-521.
3.
Rehfeld ,J. F. and Kruse-Larsen ,C. (1978). cholecystokinin in human cerebrospinal chemical determination of concentrations heterogeneity. Brain Res. 155, 19-26.
4.
Mueller,K. cystokinin Biobehav.
and Hsiao,S. as a short-term Rev. 2, 79-87.
Ljungdahl Peptidergic
Peptides and gut
,A.
,
with dual hormones.
Lundberg neruones.
,3.M. Nature
Gastrin and fluid. Immunoand molecular
(1978). Current status of cholesatiety hormone. Neurosci.
305
5.
Della-Fera,A.A. and Baile,C.A. injected in CSF decreases meal in sheep. Peptides 1, 51-54.
6.
Sturdevant,R.A.L. and Goetz,H. both stimulates and inhibits Nature 261, 713-715.
7.
Greenway satiety.
8.
Snapir ,N. and Glick,Z. size in the domestic
9.
Zetler,G. on rearing European
,F. L. Life
and Sci.
(1980). CCK-octapeptide size and daily food
(1976) Cholecystokinin human food intake.
(1977).Cholecystokinin ,G.A. 269-272.
Bray 21,
intake
(1978).Cholecystokinin fowl. PhysioI. Behav.
and
21,
(1980).Effects of cholecystokinin-like activity and hexobarbital-induced J. Pharmacol. 66, 137-139. and ptosis octapeptide
and meal 1051-1052. peptides sleep.
10.
(1980).Analgesia Zetler ,G. rulein and cholecystokinin pharmacology 19, 415-422.
11.
Telegdy,G., Fekete ,M. and Varszegi ,M. (1979). Effects of peptide hormones on the neurotransmitter metabolism of the central nervous system. In: Laszl6,F.A. (ed.) Recent Results in Peptide Hormone and Androgenic Steroid ReAkademiai I
12.
,M., Penke ,B, , Kovacs ,I<. and Telegdy, Fekete ,M. , Varszegi G. (1980).Effects of intracerebroventricular administration of cholecystokinin octapeptide sulfate ester on norepinephrine and serotonin contents of difdopamine, ferent brain structures in rats. Neuroendocrinology Letters 2, 67-72.
13.
Varszegi ,M. , Kader ,T. , Penke ,B,, , I
14.
Fekete,M., KBdar,T., Penke,B., Kovacs,K. and (1981).Influence of cholecystokinin octapeptide ester on brain monoamine metabolism in rats, Neural Transmission,in press.
15.
Fekete,M., KBdar,T., Varszegi,M., Bokor,M,, (1981). The effects and Kovacs ,K. Penke ,B. and unsulfated cholecystokinin octapeptide amine contents in rats. In: Proc. of the Union of Physiological Sciences. Akademiai in press. pest,
306
caused by (Ccl<-8).
caeNeuro-
Telegdy,G. sulfate Journal of
Telegdy,G., of sulfated on brain monoInternational Kiado, Buda-
16.
and Telegdy,G. (1981). Fekete ,M. , Balazs ,M. , Penke ,B. Influence of cholecystokinin octapeptide sulfate ester and unsulfated cholecystokinin octapeptide on conditioned feeding behaviour in rats. Physiol.Behav. in press.
17.
Ader
and de Wied,D. (1972). and passive avoidance 46-48. ,R.
active 29,
Effects learning.
of vasopressin Psychon.Sci.
on
18.
, Kovacs ,I<. , Kovacs ,L. and Balaspiri, Penke ,B. , Zarandy,M, L. (1979).Synthesis of cholecystokinin octapeptide sulfate ester. In: Kupriszewsky,G. (ed. ) Peptides 1978. Wroclaw University Publ.Co., Wroclaw, p. 581-584.
19.
(1978). Rehfeld ,3. F. and adenohypophysis.
20.
Vanderhaeghen,J.J., (1980).Immunohistochemical kininand gastrin-like physis of the rat. 1190-1194.
21.
Saito,A., (1980). terization
22.
Hays ,S.E. Paul ,S.M. site for 1, 53-62.
23.
Goltermann ,N.S., Rehfeld ,J. F. and Concentration and in vivo synthesis in subcortical regions of the rat 35, 479-483.
24.
Malesci,A., Straus,E. and Yalow,R.S. kinin-converting enzymes in brain. U.S.A. 77, 597-599.
25.
Johnson, L. R. , Stening ,G. F. Effect of sulfation on the caerulein. Gastroenterology
Localization Nature 271,
of gastrins 771-773.
to
neuro-
de Mey,J. and Gilles ,C. localization of cholecystopeptides in the brain and hypoProc.Nat. Acad.Sci. U.S.A. 77, Lotstre,F.,
Goldfine,I.D. Sankaran.H., Cholecystokinin receptors in and distribution. Science
and Williams,J.A. the brain: charac208, 1155-1156.
, Beinfeld,M.C.,
Jensen,R.T., Goodwin,F.K. (1980) Demonstration of a putative receptor cholecystokinin in rat brain. Neuropeptides
and
Petersen ,H.R. (1980). of cholecystokinin brain. J.Neurochem.
(1980).CholecystoProc.Nat.Acad.Sci.
and Grossman gastrointestinal 58, 208-216.
,M. I.
(1970). actions
of
26.
Chowdhury ,3. R. , Berkowitz ,J.M. , Praissman ,M. and Fara, J.W. (1976),Effect of sulfated and non-sulfated gastrin and octapeptide-cholecystokinin on cat gall bladder in vitro. Experientia 32, 1173-1175.
27.
Fekete,M., Bokor,M., Penke,B., ot cholecystokinin octapeptide unsulphated cholecystokinin avoidance behaviour in rats. in press.
Accepted 20th February, 1981 307
Telegdy,G. sulphate octapeptide Behavioural
(198l).Effects ester and on active Brain Research,