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Neurochemical effects of CGRP
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21 NEUROCHEHICAL EFFECTS OF CGRP
A. DRUHHELLER, D. HENARD, A. FOURNIER AND F. dOLICOEUR,Department of Ophthaimology and Departments of Psychiatry and Pharmacology, Faculty of Medi c i n e , University of SherbreoRe, Sherbrooke, Ou4bec Canada JZH 5N4 Encoded on the same gene as calcitonin~ CGRP is widely distributed in the central nervous system, where i t might act as a neurotransmitter or neuromodulator. I n t r a v e n t r i c u l a r administration of the peptide has been showe to produce a v a r i e t y of neurebehavioral effects (See dolicoeur e t a l . , this S3emposium). In order to better elucidate the role of the peptide in brain, we investigated the effects of 20 g CGRP administered to rats i n t r a v e n t r i c u l a r ] y on regional concentrations of several neurotransmitters and t h e i r metabolites. Norepinephrtne (RE), dopamine (DA}, dihydrexypbenyl acetic acid (DOPAC),homovanillic acid (HVA} as we]] as serotonin (5-HT) and 5-hydrexy indole acetic acid (5-HIAA) were quantified using an established HPLC-ECD method. Results indicate that CGRP has pervasive and d i f f e r e n t i a l e f f e c t s on biogenic amine concentrations in many regions studied. Whereas no changes occurred in the substantia nigra, striatum or septum, DA ms reduced and i t s metabo]ite, HVA markedly increased in the nucleus accumhens, suggesting an enhanced rate of turnover in th~s region. Simi]ar, though ]ess dramatic effects were noted tn the hypothalamus. S i g n i f i c a n t l y increased amounts of a l l amines and metabolites were found in the g]obus pallidus, a~ygdala and frontal cortex. F i n a l l y , concentrations of NE, DA and 5-HT were elevated in the hippocampus, while 5-HIAA was the sole metabolite affected in this region.
22 EFFECT OF CALCITONIN GENE-RELATED PEPTIDE B E H A V I O U R IN RATS. R O L E O F T R A N S M I T T E R S
ON
PASSIVE
AVOIDANCE
Annam~ria K O V A C S and G. TELEGDY, Department of Pathophysiology, Albert Szent-Gy6rgyi Medical University, Semmelweis str. i. P.O. Box 531, H-6701 Szeged, Hungary
The effects of calcitonin gene-related peptide (CGRP) on passive avoidance behaviour were studied following int racerebroventricular administration in rats. The peptide was given in a dose of ll/g pretrial, posttrial (immediately and 6 hr after testing) and 30 rain before the 24 hr testing. In order to test the possible involvement of neurotransmitters in the C G R P action the animals were pretreated with different receptor blockers in a dose which per se had no behavioural action. C G R P increased the avoidance latency in a dose-dependent manner w h e n it was given pretrial, immediately after the trial and 30 min before the 24 hr testing. H o w e v e r it was ineffective w h e n it was given 6 hr after the learning test, Propranolol (i0 mg/kg), naloxone (0.3 mg/kg) or methysergide (5 mg/kg) completely inhibited the C G R P action, while phenoxybenzamine, haloperidol, bicuculline and atropine were ineffective in such doses that could effectively block the effects of other peptides in other experiments. The data suggest that C G R P can affect learning and m e m o r y processes, and ~-adrenergic, opioid and serotoninergic mediation can be involved in this mechanism.
21 NEUROCHEHICAL EFFECTS OF CGRP
A. DRUHHELLER, D. HENARD, A. FOURNIER AND F. dOLICOEUR,Department of Ophthaimology and Departments of Psychiatry and Pharmacology, Faculty of Medi c i n e , University of SherbreoRe, Sherbrooke, Ou4bec Canada JZH 5N4 Encoded on the same gene as calcitonin~ CGRP is widely distributed in the central nervous system, where i t might act as a neurotransmitter or neuromodulator. I n t r a v e n t r i c u l a r administration of the peptide has been showe to produce a v a r i e t y of neurebehavioral effects (See dolicoeur e t a l . , this S3emposium). In order to better elucidate the role of the peptide in brain, we investigated the effects of 20 g CGRP administered to rats i n t r a v e n t r i c u l a r ] y on regional concentrations of several neurotransmitters and t h e i r metabolites. Norepinephrtne (RE), dopamine (DA}, dihydrexypbenyl acetic acid (DOPAC),homovanillic acid (HVA} as we]] as serotonin (5-HT) and 5-hydrexy indole acetic acid (5-HIAA) were quantified using an established HPLC-ECD method. Results indicate that CGRP has pervasive and d i f f e r e n t i a l e f f e c t s on biogenic amine concentrations in many regions studied. Whereas no changes occurred in the substantia nigra, striatum or septum, DA ms reduced and i t s metabo]ite, HVA markedly increased in the nucleus accumhens, suggesting an enhanced rate of turnover in th~s region. Simi]ar, though ]ess dramatic effects were noted tn the hypothalamus. S i g n i f i c a n t l y increased amounts of a l l amines and metabolites were found in the g]obus pallidus, a~ygdala and frontal cortex. F i n a l l y , concentrations of NE, DA and 5-HT were elevated in the hippocampus, while 5-HIAA was the sole metabolite affected in this region.
22 EFFECT OF CALCITONIN GENE-RELATED PEPTIDE B E H A V I O U R IN RATS. R O L E O F T R A N S M I T T E R S
ON
PASSIVE
AVOIDANCE
Annam~ria K O V A C S and G. TELEGDY, Department of Pathophysiology, Albert Szent-Gy6rgyi Medical University, Semmelweis str. i. P.O. Box 531, H-6701 Szeged, Hungary
The effects of calcitonin gene-related peptide (CGRP) on passive avoidance behaviour were studied following int racerebroventricular administration in rats. The peptide was given in a dose of ll/g pretrial, posttrial (immediately and 6 hr after testing) and 30 rain before the 24 hr testing. In order to test the possible involvement of neurotransmitters in the C G R P action the animals were pretreated with different receptor blockers in a dose which per se had no behavioural action. C G R P increased the avoidance latency in a dose-dependent manner w h e n it was given pretrial, immediately after the trial and 30 min before the 24 hr testing. H o w e v e r it was ineffective w h e n it was given 6 hr after the learning test, Propranolol (i0 mg/kg), naloxone (0.3 mg/kg) or methysergide (5 mg/kg) completely inhibited the C G R P action, while phenoxybenzamine, haloperidol, bicuculline and atropine were ineffective in such doses that could effectively block the effects of other peptides in other experiments. The data suggest that C G R P can affect learning and m e m o r y processes, and ~-adrenergic, opioid and serotoninergic mediation can be involved in this mechanism.