Neurosciences
Program

Hernandez, A.E., Smith, E.S., Cammarata, E.M., and Brady, A.M.  (2010, November).  Behavioral abnormalities in the neonatal ventral hippocampal lesion model of schizophrenia following cocaine self-administration. 

Poster presented at the Society for Neuroscience Annual Meeting, San Diego, CA.

Abstract 

Levels of recreational drug abuse are higher among patients with schizophrenia than in the general population.  Increased drug use among patients may represent attempts at self-medication, or may be a manifestation of a shared pathophysiological mechanism underlying both schizophrenia and drug addiction.  Comparably, rats with a neonatal ventral hippocampal lesion (NVHL), a developmental model of schizophrenia, are more vulnerable to the self-administration of either cocaine or methamphetamine.  Here, we investigated the short-term and long-term behavioral effects of cocaine self-administration in male rats within the NVHL model.  Rats received bilateral infusions of either ibotenic acid (NVHL group) or artificial cerebrospinal fluid (sham group) on postnatal day 7, and were allowed to grow undisturbed to adulthood (postnatal day 56 or later).  Animals were then tested at baseline on three behaviors previously shown to be disrupted in the NVHL model:  prepulse inhibition (PPI) of the acoustic startle response, spontaneous (novelty-induced) locomotion, and social interaction with a novel partner.  One week later, animals were implanted with an intravenous catheter in the external jugular vein and were trained in 14 daily 3-hour sessions to self-administer cocaine (0.75 mg/kg/infusion) on an FR1 schedule, followed by 2 days in a within-session escalating dose-response procedure (0.125, 0.25, 0.5, 1.0 mg/kg/infusion).  PPI, locomotion, and social interaction (with both a novel and a familiar partner) were then assessed again during early withdrawal (Days 3-5) and late withdrawal (Days 30-32) from cocaine.  At baseline, NVHL rats showed reduced social interaction behaviors relative to sham rats, but showed only mildly disrupted PPI and did not display hyperlocomotion.  NVHL rats did not self-administer cocaine at different rates than sham animals on either the FR1 schedule or on the dose-response procedure, similar to our previous findings with methamphetamine.  Thus, NVHL and sham rats were exposed to similar amounts of cocaine during self-administration testing.  However, behavioral differences emerged at both early and late withdrawal testing time points.  At early withdrawal, NVHL rats did not appear to show social impairments when tested with familiar partners.  In contrast, at late withdrawal, NVHL animals showed markedly disrupted PPI relative to sham animals, suggesting that cocaine exposure may have exacerbated the NVHL-induced PPI deficits.  These findings represent the first empirical investigation of the validity of the self-medication hypothesis using animal models of schizophrenia and addictive behavior.