ABSTRACT
Prepulse inhibition (PPI) of startle is a measure of sensorimotor gating that is impaired in schizophrenia. We have reported that PPI is regulated by the ventral hippocampus (VH) and that the PPI disruptive effects of the dopamine agonist apomorphine are enhanced 4 weeks after excitotoxic lesions of the VH. The mechanisms responsible for the VH influence on PPI are not understood, but have been ascribed to interactions between the VH and nucleus accumbens. In the present study, we examined whether the VH influence on PPI and its dopaminergic regulation is dependent on the integrity of the VH-accumbens projection via the fornix. First, the PPI-disruptive effects of intra-VH NMDA infusion were assessed after sham or electrolytic transection of the fornix. Second, the PPI-disruptive effects of apomorphine were assessed 1 month after excitotoxic or electrolytic lesions of the VH, or after fornix transection. Intra-VH N-methyl-D-aspartate infusion significantly disrupted PPI; this effect was unaffected by fornix lesions. The PPI-disruptive effects of apomorphine were significantly enhanced by excitotoxic or electrolytic lesions of the VH, but not by fornix transection. The influence of the VH on PPI and its dopaminergic regulation does not appear to be mediated via the fornix. The enhanced sensitivity to the PPI-disruptive effects of apomorphine after VH lesions is not dependent on excitotoxin-induced changes in the VH or its downstream projections.
Subject(s)
Apomorphine/pharmacology , Fornix, Brain/drug effects , Hippocampus/drug effects , Neural Inhibition/drug effects , Reflex, Startle/drug effects , Animals , Fornix, Brain/physiology , Hippocampus/physiology , Neural Inhibition/physiology , Rats , Rats, Sprague-Dawley , Reflex, Startle/physiologyABSTRACT
Neonatal hippocampal lesions in rats produce behavioral and neurochemical abnormalities post-puberty that are used in animal models for developmentally linked pathology in schizophrenia. In one model, adult rats exhibit enhanced sensitivity to the locomotor-activating effects of amphetamine, if they had sustained excitotoxic lesions of the ventral hippocampus on post-natal day 7. The hippocampal elements responsible for these lesion-induced developmental changes have not been fully characterized. The present study assessed the locomotor-activating effects of amphetamine in adult rats that on day 7 had sustained either sham or ibotenic acid lesions of the ventral hippocampus alone ("standard lesions"), or the ventral hippocampus plus surrounding portions of entorhinal cortex and dorsal hippocampus ("large lesions"). "Standard lesions" produced the expected "supersensitive" locomotor response to amphetamine, while "large lesions" did not. No differences between these lesion groups were observed in baseline levels of locomotor activity or habituation. These data suggest that models of enhanced behavioral sensitivity to dopamine agonists after neonatal hippocampal lesions require functionality in the entorhinal cortex and/or dorsal hippocampus. It is possible that the behavioral abnormalities in the "neonatal hippocampal lesion model" reflect, at least in part, aberrant function within spared elements of the hippocampal complex.
Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Amphetamine/pharmacology , Hippocampus/drug effects , Hippocampus/growth & development , Hyperkinesis/chemically induced , Nervous System Malformations/physiopathology , Schizophrenia/etiology , Animals , Animals, Newborn/growth & development , Animals, Newborn/metabolism , Behavior, Animal/drug effects , Behavior, Animal/physiology , Denervation , Disease Models, Animal , Hippocampus/physiology , Hyperkinesis/physiopathology , Nervous System Malformations/pathology , Rats , Rats, Sprague-Dawley , Schizophrenia/pathology , Schizophrenia/physiopathologyABSTRACT
RATIONALE: A recent report described sex differences in the effects of nicotine use and withdrawal on prepulse inhibition of acoustic startle (PPI), but no sex differences in PPI in non-smokers. OBJECTIVE: To determine whether previously reported male>female acoustic PPI reflect sex differences in smoking effects on PPI, rather than simple sex differences in the regulation of PPI. A retrospective analyses of >600 carefully screened normals tested over the past 12 years was completed. RESULTS: Male>female acoustic PPI was detected in analyses that included: 1) all subjects; or 2) self-declared non-smokers. CONCLUSIONS: Sex differences in PPI cannot be accounted for by smoking history, because they are present across a large sample of non-smoking normal controls.
Subject(s)
Reflex, Startle/physiology , Smoking/psychology , Acoustic Stimulation , Adult , Female , Humans , Male , Retrospective Studies , Sex CharacteristicsABSTRACT
The startle reflex is inhibited when the starting noise is preceded 30-500 msec by a weak prepulse. "Prepulse inhibition" (PPI) is reduced in specific neuropsychiatric disorders characterized clinically by impaired inhibition of sensory, motor, or cognitive information. PPI is sexually dimorphic, with men exhibiting significantly more PPI than women. We examined possible neuroendocrine substrates for this sex difference in PPI. The startle reflex, and a measure of visuospatial priming, were measured in 10 men, and in 46 normal women at different points in their menstrual cycle. In women, PPI was significantly reduced in the luteal vs follicular phase of the menstrual cycle. This reduction in PPI was most notable during the period corresponding to midluteal elevations of both estrogen and progesterone. In a task of visuospatial priming, follicular-phase women demonstrated a predominance of inhibition over facilitation, but this pattern reversed across the menstrual cycle.
