Neurosciences
Program

Flerlage, Jesse (2011).  Role of delta FosB in enhanced incubation of cocaine craving in the neonatal ventral hippocampal lesion model of schizophrenia. (Mentor: A.M. Brady)

Abstract 

Schizophrenia patients are 5 times more likely to develop substance use disorder (SUD) than the general population, with nearly half of patients developing some form of SUD during their lifetime. The primary addiction hypothesis proposes that the increased prevalence of SUD in schizophrenia populations is that addictive behavior is a primary symptom of the disorder stemming from overlapping neuropathology. The neonatal ventral hippocampal lesion model of schizophrenia in rat produces a variety of schizophrenia-like anomalies in behavior including aspects of enhanced self-administration of drugs of abuse. To further investigate cocaine-regulated behavior in the NVHL the incubation of cocaine craving paradigm was applied. Animals received either NVHL or SHAM lesions postnatal 6-8 days. Upon reaching adulthood animals began 10 days of 6hr/day sessions FR1 self-administration of cocaine training. Active lever responding resulted in .75 mg/kg cocaine infusion over 3.5s in conjunction with a 5s tone/light cue above active lever, followed by a 20s timeout period between infusions. On day 1 and day 30 cue-induced cocaine-seeking behavior was assessed by responding on the formerly active lever in absence of cocaine reinforcement, but the presence of cocaine-paired light-tone cue. Results indicate that both groups significantly increased their cocaine intake across the 10 sessions and NVHL animals acquired self-administration behavior at a similar rate and ingested similar amounts of cocaine during the training phase. Withdrawal responding was only found to significantly increase in a time-dependent manner among NVHL animals, meaning the typical time-dependent increase in responding expected in SHAM animals was not observed, while all other differences were insignificant.