[Effects of desipramine and clomipramine on alpha 2-adrenergic receptor function in nucleus accumbens: studies with intracerebral dialysis in freely moving rats].

The effect of alpha 2-adrenoceptor agonist, clonidine (CLN) (100 micrograms/kg, i.p.), on the noradrenalin metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG)-total in the rat nucleus accumbens after desipramine (DMI) (20 mg/kg, i.p.) and clomipramine (CMI) (20 mg/kg, i.p.) treatment was estimated in the freely moving rat by intracerebral dialysis. Locomotor activity was measured simultaneously by the Animex. Locomotor activity in the control decreased after CLN administration, in accordance with the decrease in MHPG. The difference of locomotor activity and MHPG between the single dose trial with DMI, CMI and the control did not reach statistical significance throughout the experiment. The results suggest that a single injection of DMI and CMI have not an inhibitory effect on presynaptic alpha 2-adrenergic receptor in the nucleus accumbens. Next, DMI (20 mg/kg, i.p.) and CMI (20 mg/kg, i.p.) were injected once daily for 14 days and experiments, the same method as used on the single dose trial. A difference in locomotor activity and MHPG between the chronic DMI treatment and the control reached statistical significance. A significant reduction of locomotor activity was found during the 60 min period of the experiment. In addition, a significant reduction of MHPG was found during the 30-90 min period. A difference in locomotor activity and MHPG between the chronic CMI treatment and the control reached statistical significance. A significant reduction of locomotor activity was found during the 60 min period of the experiment. In addition, a significant reduction of MHPG was found during the 30-120 min period. The results suggest that the chronic DMI treatment and the chronic CMI treatment may diminish the CLN-induced reduction of MHPG via the subsensitivity of presynaptic alpha 2-adrenergic receptor in the nucleus accumbens.