- Email: [email protected]
Neurohypophysial peptides and pigeon memory
310
NEUROHYPOPHYSIAL
PEPTIDES
AND
PIGEON
MEMORY
C. WRIGHT and A. SAHGAL, MRC N e u r o e n d o c r i n o l o g y Unit, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE. Pigeons were trained on a recognition m e m o r y task, in which t h e y h a d to d e c i d e w h e t h e r or not two s u c c e s s i v e l y p r e s e n t e d c o l o u r s t i m u l i w e r e the s a m e or d i s s i m i l a r . D i f f e r e n t d e l a y s (ranging from 0-12 sec) were also interposed between the stimuli. Typically, a p l o t of p e r f o r m a n c e v e r s u s d e l a y y i e l d s an exponentially decaying curve; drugs which improve memory will reduce the decay rate, and vice-versa. It has b e e n a r g u e d t h a t v a s o p r e s s i n (AVP) i m p r o v e s , a n d oxytocin (OT) d i s r u p t s memory. We tested the effects of intramuscular injection of AVP (4 and 40 ~g/kg), OT (i and 10 ~g/kg) and vasotocin (AVT: 2 a n d 20 ~ g / k g ) on m n e m o n i c performance. Doses were chosen on the basis of observed effects on b e h a v i o u r in the h o m e cage, a n d on k n o w n a c t i o n s on b l o o d p r e s s u r e in birds. A d r e n o c o r t i c o t r o p h i c and alpha-melanocyte stimulating hormone (ACTH a n d MSH: I0 a n d 1O0 ~g/kg) a n d chlordiazepoxide (CDP: 5 and i0 mg/kg) were also tested. Only AVT (20 %.g/kg) and CDP (5 and i0 mg/kg) had a consistent, disruptive e f f e c t on p e r f o r m a n c e , a n d t h i s was not d e l a y d e p e n d e n t . The results suggest that (a) endogenously occurring AVT possesses the ability to affect cognitive behaviour in b i r d s , a n d (b) peripheral effects may not be of critical behavioural importance, since AVP and OT had observable effects on behaviour in the home cage, but failed to alter mnemonic performance.
CHARACTERIZATION OF 3H-VASOPRESSIN BINDING TO RAT BRAIN HOMOGENATES J LAWRENCE, K LEDERIS and P POULIN, Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Among the various neuropeptides present in the central nervous system, vasopressin (AVP) is of great interest as a putative neurotransmitter apparently involved in memory, fever, pain, cardiovascular mechanisms and behaviour. Vasopressin is present in neural pathways descending from the paraventricular nucleus to the limbic system, midbrain and spinal cord. As yet, however, there has been no pharmacological characterization of central AVP receptor sites. Here, we report the use of ligand binding techniques, using 3H-AVP in rat brain homogenates, to i d e n t i f y and characterize such receptor sites. Binding assays were performed for 24 h at 4oc in an incubation medium containing Tris-HCl buffer, pH 7.4 (50 mM); MgCI2 (3 mM); bovine serum albumin (I mg/ml); bacitracin (I mg/ml), various amounts of 3H-AVP and membranes (50-100 ug/assay). 3H-AVPwas shown to bind with high a f f i n i t y to receptor sites in the rat brain. 3H-AVP binding was highest in the medulla, hippocampus, frontal cortex and cerebellum of rat brain, in descending order. This binding was saturable with respect to tissue concentration and was time, temperature and pH dependent. Binding of 3H-AVP was not inhibited by oxytocin, neurotensin, substance P, bombesin, vasoactive intestinal peptide, or by the classical neurotransmitters. In contrast we found a number of AVP analogs displaced this binding. (This work has been funded by the AHFMRand the MRC (Canada))
NEUROHYPOPHYSIAL
PEPTIDES
AND
PIGEON
MEMORY
C. WRIGHT and A. SAHGAL, MRC N e u r o e n d o c r i n o l o g y Unit, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE. Pigeons were trained on a recognition m e m o r y task, in which t h e y h a d to d e c i d e w h e t h e r or not two s u c c e s s i v e l y p r e s e n t e d c o l o u r s t i m u l i w e r e the s a m e or d i s s i m i l a r . D i f f e r e n t d e l a y s (ranging from 0-12 sec) were also interposed between the stimuli. Typically, a p l o t of p e r f o r m a n c e v e r s u s d e l a y y i e l d s an exponentially decaying curve; drugs which improve memory will reduce the decay rate, and vice-versa. It has b e e n a r g u e d t h a t v a s o p r e s s i n (AVP) i m p r o v e s , a n d oxytocin (OT) d i s r u p t s memory. We tested the effects of intramuscular injection of AVP (4 and 40 ~g/kg), OT (i and 10 ~g/kg) and vasotocin (AVT: 2 a n d 20 ~ g / k g ) on m n e m o n i c performance. Doses were chosen on the basis of observed effects on b e h a v i o u r in the h o m e cage, a n d on k n o w n a c t i o n s on b l o o d p r e s s u r e in birds. A d r e n o c o r t i c o t r o p h i c and alpha-melanocyte stimulating hormone (ACTH a n d MSH: I0 a n d 1O0 ~g/kg) a n d chlordiazepoxide (CDP: 5 and i0 mg/kg) were also tested. Only AVT (20 %.g/kg) and CDP (5 and i0 mg/kg) had a consistent, disruptive e f f e c t on p e r f o r m a n c e , a n d t h i s was not d e l a y d e p e n d e n t . The results suggest that (a) endogenously occurring AVT possesses the ability to affect cognitive behaviour in b i r d s , a n d (b) peripheral effects may not be of critical behavioural importance, since AVP and OT had observable effects on behaviour in the home cage, but failed to alter mnemonic performance.
CHARACTERIZATION OF 3H-VASOPRESSIN BINDING TO RAT BRAIN HOMOGENATES J LAWRENCE, K LEDERIS and P POULIN, Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Among the various neuropeptides present in the central nervous system, vasopressin (AVP) is of great interest as a putative neurotransmitter apparently involved in memory, fever, pain, cardiovascular mechanisms and behaviour. Vasopressin is present in neural pathways descending from the paraventricular nucleus to the limbic system, midbrain and spinal cord. As yet, however, there has been no pharmacological characterization of central AVP receptor sites. Here, we report the use of ligand binding techniques, using 3H-AVP in rat brain homogenates, to i d e n t i f y and characterize such receptor sites. Binding assays were performed for 24 h at 4oc in an incubation medium containing Tris-HCl buffer, pH 7.4 (50 mM); MgCI2 (3 mM); bovine serum albumin (I mg/ml); bacitracin (I mg/ml), various amounts of 3H-AVP and membranes (50-100 ug/assay). 3H-AVPwas shown to bind with high a f f i n i t y to receptor sites in the rat brain. 3H-AVP binding was highest in the medulla, hippocampus, frontal cortex and cerebellum of rat brain, in descending order. This binding was saturable with respect to tissue concentration and was time, temperature and pH dependent. Binding of 3H-AVP was not inhibited by oxytocin, neurotensin, substance P, bombesin, vasoactive intestinal peptide, or by the classical neurotransmitters. In contrast we found a number of AVP analogs displaced this binding. (This work has been funded by the AHFMRand the MRC (Canada))