GABAergic control of neostriatal dopamine D₂ receptor binding and behaviors in the rat

The present study assessed the influence of the GABA_A receptor agonist muscimol and the GABA_A receptor antagonist bicuculline on neostriatal dopamine D₂ receptor binding in relation to motor and exploratory behaviors in the rat.

D₂ receptor binding was measured in baseline and after challenge with either 1mg/kg muscimol or 1mg/kg bicuculline. In additional rats, D₂ receptor binding was measured after injection of saline. After treatment with muscimol, bicuculline and saline, motor and exploratory behaviors were assessed for 30min in an open field prior to administration of [¹²³I]S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide ([¹²³I]IBZM). For baseline and challenges, striatal equilibrium ratios (V₃″) were computed as estimation of the binding potential.

Muscimol but not bicuculline reduced D₂ receptor binding relative to baseline and to saline. Travelled distance, duration of rearing and frequency of rearing and of head-shoulder motility were lower after muscimol compared to saline. In contrast, duration of rearing and grooming and frequency of rearing, head-shoulder motility and grooming were elevated after bicuculline relative to saline. Moreover, bicuculline decreased duration of sitting and head-shoulder motility.

The muscimol-induced decrease of motor/exploratory behaviors can be related to an elevation of striatal dopamine levels. In contrast, bicuculline is likely to elicit a decline of synaptic dopamine, which, however, is compensated by the time of D₂ receptor imaging studies. The results indicate direct GABAergic control over D₂ receptor binding in the neostriatum in relation to behavioral action, and, thus, complement earlier pharmacological studies.