Role of cerebellar dopamine D(3) receptors in modulating exploratory locomotion and cataleptogenicity in rats.

Abstract

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 (0.3mg/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 (0.5mg/kg) of haloperidol. Furthermore, microinjection of 7-OH-DPAT into the nucleus accumbens or the dorsolateral striatum neither affected spontaneous locomotor activity nor haloperidol (0.3mg/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.

• Authors: Saki Shimizu, Ayaka Tatara, Maho Sato, Tomone Sugiuchi, Satoshi Miyoshi, Saki Andatsu, Tomoya Kizu, Yukihiro Ohno
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 50 Pg. 157-62 (Apr 03 2014) ISSN: 1878-4216 [Electronic] England
• PMID: 24368396 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• AD 6048
• Dopamine Agonists
• Dopamine Antagonists
• Indans
• Piperazines
• Pyridines
• Receptors, Dopamine D3
• Tetrahydronaphthalenes
• (5,6-dimethoxyindan-2-yl)dipropylamine
• Haloperidol
• 7-hydroxy-2-N,N-dipropylaminotetralin

Topics

• Animals
• Catalepsy (chemically induced, drug therapy)
• Cerebellum (drug effects, physiology)
• Corpus Striatum (drug effects, physiology)
• Dopamine Agonists (administration & dosage, pharmacology)
• Dopamine Antagonists (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Exploratory Behavior (drug effects, physiology)
• Haloperidol (agonists, antagonists & inhibitors, pharmacology)
• Indans (administration & dosage, therapeutic use)
• Male
• Microinjections
• Nucleus Accumbens (drug effects, physiology)
• Piperazines (administration & dosage, therapeutic use)
• Pyridines (administration & dosage, therapeutic use)
• Rats
• Receptors, Dopamine D3 (agonists, antagonists & inhibitors, physiology)
• Tetrahydronaphthalenes (administration & dosage, antagonists & inhibitors, pharmacology)