Hippocampal and cortical sensory gating in rats: Effects of quinpirole microinjections in nucleus accumbens core and shell

Sensory processing disturbances, as measured in the P50/sensory gating para digm, have been linked to aberrant auditory information processing and sens ory overload in schizophrenic patients. In this paradigm, the response to t he second of paired-click stimuli is attenuated by an inhibitory effect of the first stimulus. Sensory gating has been observed in most healthy human subjects and normal laboratory rats. Because mesolimbic dopamine has been i mplicated in other filtering disturbances such as prepulse inhibition of th e acoustic startle response and given the fact that amphetamine and apomorp hine have been shown to disrupt gating, this study was performed to investi gate the role of mesolimbic dopamine in sensory gating. The dopamine D2 rec eptor agonist quinpirole (10 mug/0.5 mul) was injected bilaterally in nucle us accumbens core and shell and effects on cortical and hippocampal sensory gating were investigated. Also, effects of the dopamine D2 receptor antago nist haloperidol (0.1 mg/kg, subcutaneously) as pretreatment were studied. First, quinpirole significantly reduced both the amplitude to the first cli ck and gating as measured in the cortex and in the hippocampus. There was a tendency for the quinpirole effects on hippocampal gating to be more prono unced in rats injected in the shell. Secondly, haloperidol did not antagoni ze effects of quinpirole on hippocampal parameters, whereas haloperidol pre treatment fully antagonized quinpirole effects on cortical parameters. In conclusion, gating can be significantly reduced when a dopamine agonist is specifically targeted at mesolimbic dopamine D2 receptors. However, an i mportant consideration is that the dopaminergic effects in the present stud y on gating are predominantly mediated by the effects on the amplitude to t he first click. This has also been suggested for systemic amphetamine injec tions in rats and schizophrenic patients. This casts doubt on whether dopam ine receptor activation affects the putative inhibitory process between the first and the second stimulus. (C) 2001 IBRO. Published by Elsevier Scienc e Ltd. All rights reserved.