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Some anticonvulsant drugs alter monoamine‐mediated behaviour in mice in ways similar to electroconvulsive shock; implications for antidepressant therapy
Author(s) -
Green A. Richard,
Johnson Pauline,
Mountford Judith A.,
Nimgaonkar Vishwajit L.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb12918.x
Subject(s) - anticonvulsant , diazepam , carbamazepine , pharmacology , apomorphine , phenytoin , chemistry , anesthesia , medicine , dopaminergic , dopamine , epilepsy , psychiatry
1 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 β‐adrenoceptor and 5‐HT 2 receptor number have been examined. 2 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‐HT 2 receptor number in frontal cortex. 3 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. 4 Repeated Na valproate (400 mg kg −1 , i.p.) also increased the 5‐HTP‐induced head‐twitch response and 5‐HT 2 receptor number in the frontal cortex when given twice daily for 14 days, but no behavioural enhancement was seen after 10 days' treatment. 5 Diazepam (1.25 mg kg −1 i.p.) twice daily for 14 days increased the head‐twitch response and 5‐HT 2 receptor number. 6 Repeated progabide and valproate (but not diazepam) administration attenuated the sedation response to the α 2 ‐adrenoceptor agonist, Clonidine (0.15 mg kg −1 ) but neither drug altered β‐adrenoceptor number in the cerebral cortex. 7 No changes in apomorphine‐induced locomotor behaviour were seen after progabide, valproate or diazepam. 8 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. 9 Like repeated electroconvulsive shock (ECS), progabide altered the head‐twitch response, clonidine‐induced sedation response and 5‐HT 2 receptor number. Unlike repeated ECS, it did not alter β‐adrenoceptor number or the apormorphine‐induced locomotor response. These data suggest that ECS may produce some changes in monoamine function by altering GABA metabolism as has previously been postulated.