Anxiogenic-like effects induced by stimulation of dopamine receptors

We considered the increase in latency for entering into a white-lightened compartment from a black one as an index of anxiety for Swiss albino mice. This has been validated with several reference anxiogenic drugs [pentylenetetrazole, yohimbine, dexamphetamine, and methyl-beta-carboline-3-carboxylate (beta-CCM)]. On this test, the effects of various indirect or direct dopamine (DA) agonists have been investigated, as well as the respective involvement of D1 and D2 dopamine receptors. Dexamphetamine, the specific DA uptake inhibitor 1-[2-(diphenylmethoxy)-ethyl]4-(3-phenyl propenyl)-piperazine (GBR 12783), and the mixed DA/norepinephrine uptake inhibitor N-[1-(2-benzo(b)thiophenyl)-cyclohexyl]piperidine (GK 13) dose dependently increased the entering latency. This effect was shared by the D2 DA agonist RU 24926. The partial agonist of D1 DA receptors SK&F38393 had a significant although moderate efficacy. Their association led at best to an additive synergy. The antagonist of D1 DA receptors SCH23390 shortened the entering latency. The anxiogenic effect of GBR 12783 was antagonized by haloperidol and SCH23390. It is concluded that an anxiogenic-like effect is linked to an increase in dopaminergic transmission involving both D1 and D2 dopamine receptors.