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 sensorimotor gating that is impaired in schizophrenia patients and dopamine agonist-treated rats. Previous reports demonstrated an enhanced sensitivity to the prepulse inhibition-disruptive effects of the D(1)/D(2) agonist apomorphine in adult rats four weeks after cytotoxic lesions of the hippocampus, but 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 schizophrenia, studies now assessed specific features of this effect of hippocampus lesions on prepulse inhibition in rats. The enhanced prepulse inhibition-disruptive effects of apomorphine in ventral hippocampus-lesioned rats were unaffected by startle pulse intensity, suggesting an independence of this lesion effect from potential ceiling effects of elevated startle magnitude. 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 after lesions restricted to the dorsal hippocampus; in contrast, these lesions significantly increased "no-drug" levels of prepulse inhibition. Ventral hippocampus-lesioned rats exhibited a significant reduction in prepulse inhibition 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 ventral hippocampus dysfunction to the neurobiology of impaired sensorimotor gating in neuropsychiatric populations.
Swerdlow
N R
NR
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla CA 92093-0804, USA. nswerdlow@ucsd.edu
Taaid
N
N
Halim
N
N
Randolph
E
E
Kim
Y K
YK
Auerbach
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D018491:Dopamine Agonists; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001058:Apomorphine