Effects of galanin on 8-OH-DPAT induced decrease in body temperature and brain 5-hydroxytryptamine metabolism in the mouse.
Central administration of galanin dose-dependently (minimum effective dose, M.E.D. = 1 nmol) blocked the hypothermia induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg s.c.), in mice. This inhibitory effect was reversed by pretreatment with the galanin receptor antagonist galantide (0.3 nmol) and also by pretreatment with the ATP-sensitive potassium channel blockers glibenclamide (10 nmol) and gliquidone (10 nmol). The hypothermic response to 8-OH-DPAT was also blocked by the 5-HT1A receptor antagonist (N-(2,4(2-methoxyphenyl)-1-piperazinyl)ethyl-N-(2-pyridinyl)cyclohexane, (WAY 100,635, M.E.D. = 0.01 mg/kg s.c.), and the centrally acting muscarinic receptor antagonist scopolamine (M.E.D. = 10 mg/kg i.p.) but not the peripheral muscarinic receptor antagonist N-methylscopolamine. 8-OH-DPAT (0.5 mg/kg s.c.) also decreased cortical and hypothalamic 5-HT (5-hydroxytryptamine, serotonin) metabolism, an effect which was not blocked by pretreatment with galanin (0.3-3 nmol intracerebroventricular, i.c.v.). Neither did galanin (0.03-3 nmol/5 microliters i.c.v.) affect basal 5-HT metabolism in these brain regions. Furthermore, pretreatment in vitro of mouse cortical membranes with galanin (10 or 1000 nM) had no effect on 5-HT1A receptor affinity, Bmax or pharmacology determined using [3H]8-OH-DPAT. These results suggest that the inhibition of 8-OH-DPAT induced hypothermia by galanin is probably not mediated by an interaction with 5-HT1A receptors but more likely by blocking the indirect activation by 8-OH-DPAT of central cholinergic pathways involved in temperature regulation.
Patel
S
S
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Hutson
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PH
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D019004:Galanin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D010879:Piperazines; D015221:Potassium Channels; D011725:Pyridines; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019004:Galanin; D012601:Scopolamine