title: Some anticonvulsant drugs alter monoamine-mediated behaviour in mice in ways similar to electroconvulsive shock; implications for antidepressant therapy.
abstract: The effects in mice of administration of the anticonvulsants, progabide, sodium valproate, diazepam, carbamazepine and phenytoin on 5-hydroxytryptophan (5-HTP)-induced head-twitch, apomorphine-induced locomotion, clonidine-induced sedation, and beta-adrenoceptor and 5-HT2 receptor number have been examined. Repeated progabide administration (400 mg kg-1, i.p. twice daily for 14 days) enhanced the head-twitch response the effect lasting for over 8 days after the last dose, and also increased 5-HT2 receptor number in frontal cortex. Progabide (400 mg kg-1, i.p.) enhanced the head-twitch response when given once daily for 10 days and when given intermittently (5 times over 10 days) but not after 1 day of administration. Repeated Na valproate (400 mg kg-1, i.p.) also increased the 5-HTP-induced head-twitch response and 5-HT2 receptor number in the frontal cortex when given twice daily for 14 days, but no behavioural enhancement was seen after 10 days' treatment. Diazepam (1.25 mg kg-1, i.p.) twice daily for 14 days increased the head-twitch response and 5-HT2 receptor number. Repeated progabide and valproate (but not diazepam) administration attenuated the sedation response to the alpha 2-adrenoceptor agonist, clonidine (0.15 mg kg-1) but neither drug altered beta-adrenoceptor number in the cerebral cortex. No changes in apomorphine-induced locomotor behaviour were seen after progabide, valproate or diazepam. Repeated carbamazepine (20 mg kg-1) or phenytoin (40 mg kg-1) administration failed to alter any of the biochemical or behavioural parameters listed above. Like repeated electroconvulsive shock (ECS), progabide altered the head-twitch response, clonidine-induced sedation response and 5-HT2 receptor number. Unlike repeated ECS, it did not alter beta-adrenoceptor number or the apomorphine-induced locomotor response. These data suggest that ECS may produce some changes in monoamine function by altering GABA metabolism as has previously been postulated.
authors.forename: A R
authors.initials: AR
authors.lastname: Green
authors.forename: P
authors.initials: P
authors.lastname: Johnson
authors.forename: J A
authors.initials: JA
authors.lastname: Mountford
authors.forename: V L
authors.initials: VL
authors.lastname: Nimgaonkar
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001679:Biogenic Amines / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004597:Electroshock; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D001679:Biogenic Amines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; C017985:progabide; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D006916:5-Hydroxytryptophan; D003000:Clonidine; D001058:Apomorphine; D003975:Diazepam