Hippocampal lesions enhance startle gating-disruptive effects of apomorphine in rats: A parametric assessment

Prepulse inhibition of the startle reflex is an operational measure of sens orimotor gating that is impaired in schizophrenia patients and dopamine ago nist-treated rats. Previous reports demonstrated an enhanced sensitivity to the prepulse inhibition-disruptive effects of the D-1/D-2 agonist apomorph ine in adult rats four weeks after cytotoxic lesions of the hippocampus, bu t left unanswered several important questions regarding the nature of this apparent lesion-induced dopamine supersensitivity. Because of the potential importance of this model to current theories of the pathophysiology of sch izophrenia, studies now assessed specific features of this effect of hippoc ampus lesions on prepulse inhibition in rats. The enhanced prepulse inhibit ion-disruptive effects of apomorphine in ventral hippocampus-lesioned rats were unaffected by startle pulse intensity, suggesting an independence of t his lesion effect from potential ceiling effects of elevated startle magnit ude. These lesion effects were observed four weeks post-lesion, but not two weeks post-lesion, suggesting a delayed development of this phenomenon. No enhancement of apomorphine sensitivity was observed in rats four weeks aft er lesions restricted to the dorsal hippocampus; in contrast, these lesions significantly increased "no-drug" levels of prepulse inhibition. Ventral h ippocampus-lesioned rats exhibited a significant reduction in prepulse inhi bition after subthreshold doses of either the selective D-2-family agonist quinpirole or the partial D-1 agonist SKF 38393, suggesting that activation of either receptor family is adequate for the expression of this effect of ventral hippocampus lesions. This may be an important paradigm for understanding the contribution of ven tral hippocampus dysfunction to the neurobiology of impaired sensorimotor g ating in neuropsychiatric populations. (C) 2000 IBRO. Published by Elsevier Science Ltd.