Abstract
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 GABAB 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 GABAB 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 GABAB 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 GABAB 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 GABAB 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 GABAB receptors as an important substrate for sensorimotor gating control in DBA/2J mice and encourage further investigations on the role of GABAB receptors in sensorimotor gating, as well as in the pathophysiology of psychotic disturbances.
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M. Paola Castelli, Giampaolo Mereu, and Francesco Marrosu have contributed equally to the study.
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Bortolato, M., Frau, R., Orrù, M. et al. Activation of GABAB receptors reverses spontaneous gating deficits in juvenile DBA/2J mice. Psychopharmacology 194, 361–369 (2007). https://doi.org/10.1007/s00213-007-0845-5
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DOI: https://doi.org/10.1007/s00213-007-0845-5