Corticosterone modulates dopamine and serotonin1A receptor mediated regulation of prepulse inhibition and startle in male rats

The aim of this project was to investigate the role of stress in neurotransmitter modulation of prepulse inhibition (PPI), a model of sensorimotor gating which is disrupted in schizophrenia and other illnesses. We studied the effect of adrenalectomy (ADX) and low and high levels of corticosterone (CORT) replacement on the effect of pharmacological modulators of PPI in rats. In ADX rats treated with a high dose of CORT (CORT200) the disruption of PPI caused by acute treatment with the dopamine receptor agonist, apomorphine, was significantly enhanced compared to ADX rats implanted with a control cholesterol pellet. On the other hand, CORT200 rats were less sensitive to the effect of the serotonin_1A receptor agonist, 8-OH-DPAT, while ADX rats implanted with a lower dose of CORT (CORT50) showed enhanced responding to this treatment. There were no differential effects on baseline PPI, or changes in startle or habituation of startle that could explain the effects on PPI. These data suggest that prolonged CORT treatment induces a major shift in dopaminergic and serotonergic mechanisms involved in the regulation of PPI. ADX and CORT replacement were found to have no effect on dopamine D₂ receptor densities in the nucleus accumbens (NAc), striatum or cingulate cortex, suggesting that our current observations are not due to changes in the levels of these receptors. These data may provide new insight into the role of stress in psychosis.