Nicotine sensitization in a rodent model of schizophrenia: A comparison of adolescents, adults, and neurotrophic factors.

摘要

The behavioral effects of nicotine on locomotor activity in a rodent model of psychosis were analyzed. This model is based on neonatal quinpriole treatment (a dopamine D2/D3 agonist) which causes increased D2 receptor sensitivity, a phenomenon known as D2 priming that is common in schizophrenia. D2-primed adolescent rats did not demonstrate nicotine-induced hypoactivity early in training, and males demonstrated more rapid sensitization to nicotine as compared to controls administered nicotine. D2-primed females administered nicotine demonstrated increased stereotypic behavior. D2-primed adult rats given nicotine demonstrated significantly more robust sensitization to nicotine than controls given nicotine. Brain-derived neurotrophic factor (BDNF) was analyzed in the nucleus accumbens. BDNF was significantly increased in nicotine treated adolescent females but was not affected in males. Nicotine alleviated BDNF deficits in D2-primed adults. These results suggest that sensitization to nicotine in D2-primed rats is age dependent, and nicotine induced changes in BDNF that is age and sex-dependent.