Anxiolytic effects of dopamine receptor ligands: I. involvement of dopamine autoreceptors

Abstract

The anxiolytic-like properties of dopamine agonists and antagonists with different receptor profiles were investigated in the ultrasonic vocalization test in rats after subcutaneous administration. Only dopamine D₂ receptor agonists inhibited ultrasonic vocalization with the following ED₅₀ values: apomorphine (0.07 $\text{mg}\text{kg}$), quinelorane (0.01 $\text{mg}\text{kg}$), quinpirole (0.04 $\text{mg}\text{kg}$), pramipexole (0.09 $\text{mg}\text{kg}$), roxindole (0.04 $\text{mg}\text{kg}$), talipexole (0.04 $\text{mg}\text{kg}$), (±)-7-OH-DPAT (0.05 $\text{mg}\text{kg}$), (±)-PPHT (0.03 $\text{mg}\text{kg}$), (−)-TNPA (0.06 $\text{mg}\text{kg}$), PD128907 (0.13 $\text{mg}\text{kg}$). The D₂ antagonists haloperidol, mazapertine, raclopride, remoxipride, L745870, U99194A, U101958 and S(−)-DS121, the partial agonists PD143188 and preclamol, the selective D₁ agonist R(+)-SKF38393 and the D₁ antagonist SCH23390, and the uptake inhibitors GBR12909, GBR12935 and indatraline lacked significant inhibitory effects on ultrasonic vocalization. Because at least some of the D₂ receptor agonists investigated have selectivity for dopamine autoreceptors, it is speculated that the dopamine autoreceptor may be a target for the development of new antianxiety drugs.