Effects of drugs affecting the noradrenergic system on convulsions in the quaking mouse.
Handling-induced convulsions in the quaking mouse can be blocked by: phenobarbital, pentobarbital or phenytoin; postsynaptic alpha-adrenoceptor agonists (noradrenaline, phenylephrine, CRL 40028); presynaptic alpha-adrenoceptor blockers (yohimbine, mianserine); catecholamine liberating agent (amphetamine); noradrenaline reuptake inhibitors (cocaine, imipramine, desipramine). Moreover, the protective effect of yohimbine was antagonized by clonidine, prazosin or alpha-methylparatyrosine, and the protective effect of CRL 40028 was antagonized by prazosin but not by alpha-methyltyrosine. Drugs acting by other mechanisms (pilocarpine, atropine, trihexyphenidyl, (--)-5-HTP, methysergide, pimozide, clonidine, alpha-methyl DOPA, prazosin, isoprenaline, salbutamol) did not protect against convulsions. A slight protection was obtained with high doses of apomorphine and also with (+/-)-propranolol. This effect is probably not related to blockade of beta-adrenoceptors because the same effect was obtained with (+)propranolol. In young quaking mice, where susceptibility to convulsions is low, both postsynaptic alpha-adrenoceptor blockers and presynaptic alpha-adrenoceptor antagonist lowered the convulsive threshold. Thus, this seems to constitute an interesting model for the in vivo study of substances which affect the central alpha-adrenoceptors either pre- or postsynaptically.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004347:Drug Interactions; D006234:Handling, Psychological / Q000502:physiology; D008297:Male; D051379:Mice; D008821:Mice, Quaking; D009638:Norepinephrine / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D012640:Seizures / Q000503:physiopathology*; D012701:Serotonin / Q000502:physiology
D000927:Anticonvulsants; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D012701:Serotonin; D009638:Norepinephrine