Sensory processing disturbances, as measured in the P50/
sensory gating paradigm, have been linked to aberrant auditory information processing and
sensory overload in
schizophrenic patients. In this paradigm, the response to the 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 implicated in other filtering disturbances such as
prepulse inhibition of the
acoustic startle response and given the fact that
amphetamine and
apomorphine have been shown to disrupt gating, this study was performed to investigate the role of mesolimbic
dopamine in
sensory gating. The
dopamine D2 receptor agonist quinpirole (10 microg/0.5 microl) was injected bilaterally in
nucleus accumbens core and shell and effects on cortical and
hippocampal sensory gating were investigated. Also, effects of the
dopamine D2 receptor antagonist
haloperidol (0.1 mg/kg,
subcutaneously) as pretreatment were studied. First,
quinpirole significantly reduced both the amplitude to the first click 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 pronounced in rats injected in the shell. Secondly,
haloperidol did not antagonize effects of
quinpirole on
hippocampal parameters, whereas
haloperidol pretreatment 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 important consideration is that the
dopaminergic effects in the present study on gating are predominantly mediated by the effects on the amplitude to the first click. This has also been suggested for systemic
amphetamine injections in rats and
schizophrenic patients. This casts doubt on whether
dopamine receptor activation affects the putative
inhibitory process between the first and the second stimulus.
