Alpha-1-adrenergic receptors mediate sensorimotor gating deficits producedby intracerebral dizocilpine administration in rats

Prepulse inhibition refers to the inhibition by a weak prepulse of the star tle response to an intense stimulus. Prepulse inhibition is thought to prov ide an operational measure of sensorimotor gating, a putative central inhib itory process by which an organism filters information from its environment . Prepulse inhibition deficits are observed in schizophrenia patients and i n rats treated with psychotomimetic compounds, such as the non-competitive N-methyl-D-aspartate antagonists phencyclidine or dizocilpine maleate. In r ats, phencyclidine-induced prepulse inhibition deficits are blocked by cloz apine, olanzapine and quetiapine, which are multireceptor antagonists and a typical antipsychotics, or by prazosin, which is a selective alpha(1)-adren ergic antagonist. The dorsal hippocampus and amygdala are two of the brain regions shown to contribute to the disruption of prepulse inhibition produc ed by non-competitive N-methyl-D-aspartate antagonists. The present study t ested the hypotheses that quetiapine or prazosin would prevent deficits in prepulse inhibition produced by dizocilpine infusion into the dorsal hippoc ampus or amygdala. In separate groups of rats, either quetiapine (0 or 5.0 mg/kg, s.c.) or prazosin (0 or 1.0 mg/kg, i.p.) was administered 15 min pri or to bilateral infusion of dizocilpine (0 or 6.25 mu g/0.5 mu l/side) into either the dorsal hippocampus or amygdala. Rats were placed into startle c hambers immediately after intracerebral drug infusion and prepulse inhibiti on was assessed. Confirming previous studies, prepulse inhibition was decre ased after either intra-dorsal hippocampus or intra-amygdala infusions of d izocilpine. Both quetiapine and prazosin blocked the prepulse inhibition de ficits produced by intracranial dizocilpine administration. Startle reactiv ity was increased by dizocilpine infusion into either region; these effects were not blocked by either quetiapine or prazosin. These results indicate that non-competitive N-methyl-D-aspartate antagonist s may disrupt sensorimotor gating via actions within the dorsal hippocampus or amygdala, and that alpha(1)-adrenergic receptors distal to these sites might mediate this effect. (C) 1999 IBRO. Published by Elsevier Science Ltd .