Role of cerebellar dopamine D3 receptors in modulating exploratory locomotion and cataleptogenicity in rats

Dopamine D-3 receptors are highly expressed in the cerebellum; however, their pathophysiological functions are not fully understood. Here, we conducted microinjection studies to clarify the role of cerebellar D-3 receptors in modulating locomotion and cataleptogenicity in rats. Microinjection of the preferential D-3 agonist 7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OH-DPAT) into lobe 9 of the cerebellum significantly reduced spontaneous locomotor activity with a U-shaped dose-response curve. The intracerebellar microinjection of 7-OH-DPAT did not elicit catalepsy by itself, but markedly potentiated catalepsy induction with a low dose (0.3 mg/kg) of haloperidol. The catalepsy enhancement by 7-OH-DPAT occurred in a dose-dependent manner and was not associated with the locomotor inhibition. U-99194A (a selective D-3 antagonist) or AD-6048 (a preferential D-3 vs. D-2 antagonist) antagonized both the catalepsy enhancement and the locomotor inhibition with 7-OH-DPAT. In addition, U-99194A and AD-6048 per se significantly alleviated catalepsy induced by a high dose (0.5 mg/kg) of haloperidol. Furthermore, microinjection of 7-OH-DPAT into the nucleus accumbens or the dorsolateral striatum neither affected spontaneous locomotor activity nor haloperidol (0.3 mg/kg)-induced catalepsy. The present results illustrate for the first time the role of cerebellar D-3 receptors in modulating cataleptogenicity of antipsychotic agents, implying that blockade of cerebellar D-3 receptors contributes to the reduction of extrapyramidal side effects. (C) 2013 Elsevier Inc. All rights reserved.