title: The ventral hippocampal regulation of prepulse inhibition and its disruption by apomorphine in rats are not mediated via the fornix.
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.
authors.affiliation: UCSD Department of Psychiatry, 9500 Gilman Drive, 92037-0804, La Jolla, CA, USA. nswerdlow@ucsd.edu
authors.forename: N R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: J M
authors.initials: JM
authors.lastname: Shoemaker
authors.forename: H R
authors.initials: HR
authors.lastname: Noh
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: I
authors.initials: I
authors.lastname: Gaudet
authors.forename: M
authors.initials: M
authors.lastname: Munson
authors.forename: S
authors.initials: S
authors.lastname: Crain
authors.forename: P P
authors.initials: PP
authors.lastname: Auerbach
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D020712:Fornix, Brain / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology
chemical_list: D001058:Apomorphine