Neurosciences
Program

Flynn, E.D., Miller, E.D., Palacorolla, H.L., Tatem, K.S., and Brady, A.M. (2012, October).  Self-administration of cocaine does not alleviate behavioral abnormalities in the neonatal ventral hippocampal lesion model of schizophrenia. 

Poster presented at the Society for Neuroscience Annual Meeting, New Orleans, LA.

Abstract 

Patients with schizophrenia abuse drugs at higher rates than the general population, which may reflect self-medication attempts aimed at alleviating disease symptoms and/or medication side effects.  Rats with a neonatal ventral hippocampal lesion (NVHL), a developmental model of schizophrenia, show enhanced drug self-administration.  If this represents a process analogous to self-medication, then behavioral abnormalities in NVHL rats (which correspond to clinical symptoms) should be alleviated following drug exposure.  Here, we investigated the short- and long-term behavioral effects of self-administered (SA) or experimenter-administered (EA) cocaine, or self-administered sucrose in male rats within the NVHL model.  Rats received bilateral hippocampal infusions of ibotenic acid (NVHL) or artificial CSF (sham) on postnatal day 7.  At postnatal day 58 or later (baseline), adult animals were tested on three behaviors typically disrupted in NVHL rats:  prepulse inhibition (PPI), spontaneous locomotion, and social interaction.  One week later, SA animals were catheterized in the external jugular vein and self-administered cocaine (0.75 mg/kg/infusion) on an FR1 schedule for 14 days followed by 2 days in a dose-response session (0.125, 0.25, 0.5, 1.0 mg/kg/infusion), or self-administered saline (0.1 ml/infusion) for 16 days. EA animals underwent a sham catheter implantation and were given 16 days of escalating dose cocaine injections (5 mg/kg to 20 mg/kg, i.p.) to match cocaine intake of the SA animals, or 16 days of saline injections (1 ml/kg, i.p.).  Sucrose animals were food-restricted and self-administered sucrose on an FR1 schedule for 14 days followed by 2 days in a modified dose-response session (1, 2, 4 pellets per response).  PPI, locomotion, and social interaction were assessed again during early (Days 3-6) and late withdrawal (Days 30-33) from cocaine or saline.  At baseline, NVHL rats showed reduced social interaction and disrupted PPI relative to sham rats, but did not display hyperlocomotion.  Exposure to either SA or EA cocaine did not alter PPI or locomotion, but higher intake of SA cocaine predicted impaired PPI (in both NVHL and sham rats) during late withdrawal.  The basal startle response was enhanced during withdrawal in all SA cocaine animals, but not in any other groups.  Unexpectedly, PPI deficits in NVHL animals were alleviated during late withdrawal following sucrose self-administration.  Overall, little evidence was found for lasting effects of cocaine exposure, whether self- or experimenter-administered, and no evidence was found to support the self-medication hypothesis of drug abuse in schizophrenia within this animal model.