Long-term imipramine effects are prevented by NMDA receptor blockade

Abstract

Long-term exposure to different antidepressant treatments induces increased motor response to central stimulants, due to a selective supersensitivity of dopamine D 2 receptors in the limbic areas. Such an effect is accompanied by down-regulation of dopamine D 1 receptor number, and by a decreased response of adenylyl cyclase to dopamine stimulation in the limbic system. Moreover, the number of β-adrenergic receptors and the response of adenylyl cyclase to β-adrenergic stimulation in the cortex result to be reduced. The present data confirms that imipramine (10 mg/kg twice a day for 3 weeks) produces such effects, and shows that the co-administration of imipramine with MK-801 (administered by a subcutaneously implanted minipump delivering 0.05 mg/kg/day of the compound) prevented the occurence of both the behavioral supersensitivity to quinpirole, and the decrease of dopamine D 1 and β-adrenergic receptor function.