期刊
PSYCHOPHARMACOLOGY
卷 194, 期 3, 页码 361-369出版社
SPRINGER
DOI: 10.1007/s00213-007-0845-5
关键词
DBA/2J; baclofen; GABA(B) receptor; prepulse inhibition; startle reflex; autoradiography
Rationale Gamma-amino-butyric acid (GABA)(B) receptors play a key role in the pathophysiology of psychotic disorders. We previously reported that baclofen, the prototypical GABA(B) agonist, elicits antipsychotic-like effects in the rat paradigm of prepulse inhibition (PPI) of the startle, a highly validated animal model of schizophrenia. Objectives We studied the role of GABA(B) receptors in the spontaneous PPI deficits displayed by DBA/2J mice. Materials and methods We tested the effects of baclofen (1.25-5 mg/kg, intraperitoneal [i.p.]) in DBA/2J and C57BL/6J mice, in comparison to the antipsychotic drugs haloperidol (1 mg/kg, i.p.) and clozapine (5 mg/kg, i.p.). Furthermore, we investigated the expression of GABA(B) receptors in the brain of DBA/2J and C57BL/6J mice by quantitative autoradiography. Results Baclofen dose-dependently restored PPI deficit in DBA/2J mice, in a fashion similar to the antipsychotic clozapine (5 mg/kg, i.p.). This effect was reversed by pretreatment with the GABA(B) antagonist SCH50211 (50 mg/kg, i.p.). In contrast, baclofen did not affect PPI in C57BL/6J mice. Finally, quantitative autoradiographic analyses assessed a lower GABA(B) receptor expression in DBA/2J mice in comparison to C57BL/6J controls in the prefrontal cortex and hippocampus but not in other brain regions. Conclusions Our data highlight GABA(B) receptors as an important substrate for sensorimotor gating control in DBA/2J mice and encourage further investigations on the role of GABA(B) receptors in sensorimotor gating, as well as in the pathophysiology of psychotic disturbances.
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