Behavioral predictors of alcohol drinking in a neurodevelopmental rat model of schizophrenia and co-occurring alcohol use disorder

Alcohol use disorder commonly occurs in patients with schizophrenia and contributes greatly to its morbidity. Unfortunately, the neural and behavioral underpinnings of alcohol drinking in these patients are not well understood. In order to begin to understand the cognitive and reward-related changes that may contribute to alcohol drinking, this study was designed to address: 1) latent inhibition; 2) conditioning; and 3) extinction of autoshaping in a neurodevelopmental rat model with relevance to co-occurring schizophrenia and alcohol use disorders, the neonatal ventral hippocampal lesioned (NVHL) rat. NVHL lesions (or sham surgeries) were performed on post-natal day 7 (PND7) and animals were given brief exposure to alcohol during adolescent (PND 28-42). Latent inhibition of autoshaping, conditioning and extinction were assessed between PND 72-90. On PND90 animals were given alcohol again and allowed to establish stable drinking. Latent inhibition of autoshaping was found to be prolonged in the NVHL rats; the NVHL rats pre-exposed to the lever stimulus were slower to acquire autoshaping than sham pre-exposed rats. NVHL rats that were not pre-exposed to the lever stimulus did not differ during conditioning, but were slower to extinguish conditioned responding compared to sham controls. Finally, the NVHL rats from both groups drank significantly more alcohol than sham rats, and the extent of latent inhibition predicted future alcohol intake in the pre-exposed animals. These findings suggest that the latent inhibition of autoshaping procedure can be used to model cognitive- and reward-related dysfunctions in schizophrenia, and these dysfunctions may contribute to the development of co-occurring alcohol use.