Effects of antidepressants in the forced swimming test (report 4)

Abstract

Functional role of β-adrenergic mechanisms on the immobi lity-reducingaction of desipramine (DMI) in the forced swimming test was examined. Intracerebro-ventricular injections of isoproterenol (Iso) and two selective β1adrenergic blockers,atenolol (Ate) and practolol (Pra), but not a β2radrenergic blocker, IPS 339(IPS), diminished and potentiated the action of DMI(20 mg/kg,i.p.x3), respectively. The effect of Iso was almost completely blocked by pretreatment with Ate and Pra, but not by IPS. In contrast with β1adrenergic blockers,a non selective β1-adrenergic blocker,dl-propranolol,did not influence the action of DMI, but completely antagonized the effect of Iso. The potentiating effect of Ate or Pra was inhibited by IPS,but not by d-propranolol. As in the case of Iso, subcutaneous injection of clonidine(Clo) suppressed the action of DMI. The effect of do,but not that of Iso,was almost completely blocked by yohimbine. Chronic treatment(10 mg/kg,i.ρ, twice daily for 15 days) with DMI enhanced the action of the drug as compared to acute administration. The potentiation of the action of DMI by chronic treatment with the drug was inhibited by combined administration of Ate or Pra. On the other hand, a single injection of DMI,which had no effect when given alone, reduced the duration of immobility in rats treated chronically with ISO. These results suggest that β1adrenergi c mechanisms have an inhibitory effect on the immobility-reducing action of DMI in the forced swimming test, but the potentiating effect of Ate and Pra is inhibited by simul taneous blockade of both β1 and β2-adrenoceptors. It is also suggested that reduced function of the inhibitory β1adrenergic mechanisms is responsible for the potentiation of the action of DMI by chronic administration of the drug.