Evidence that muscimol acts in the forced swimming test by activating the rat dopaminergic system.
Muscimol as well as catecholaminergic drugs reduce immobility time in the forced swimming test. In view of the fact that GABAergic drugs may facilitate some brain catecholaminergic functions, we investigated as to whether or not muscimol would reduce immobility time through activation of catecholaminergic mechanisms. The effect of muscimol (2 mg/Kg i.p.) on reduction of immobility time was prevented by intraperitoneal alpha-methyl-para-tyrosine (250 mg/Kg i.p.), which reduces brain catecholamine content, haloperidol (0.5 mg/Kg) and sulpiride (100 and 50 mg/Kg), antidopaminergic drugs, and meta-chlorphenyl-piperazine (0.6 and 1.25 mg/Kg), a serotonergic agonist, but not by clonidine (0.1 mg/Kg), an alpha2-adrenoceptor agonist, d, 1-propranolol (5 mg/Kg), an antagonist of beta-adrenergic receptors, or subcutaneous prazosin (3 mg/Kg), an alpha1-adrenolytic drug. Our findings indicate that a) muscimol reduces immobility time by stimulating dopaminergic neurons and b) activation of the serotonergic system antagonizes muscimol effect.
A. Menarini, S.a.S. Pharmaceuticals, Research Department, Firenze, Italy.
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Evangelista
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Borsini
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Meli
D000818:Animals; D001921:Brain / Q000502:physiology; D002395:Catecholamines / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009118:Muscimol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013550:Swimming; D013997:Time Factors
D002395:Catecholamines; D009118:Muscimol; D004298:Dopamine