NICOTINE SELF-ADMINISTRATION IN RATS - STRAIN AND NICOTINE PREEXPOSURE EFFECTS ON ACQUISITION

Nicotine has been shown to maintain intravenous self-administration be haviour in humans and laboratory animals. However, factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences and effects of pre-exposure to nicot ine have not been examined. Male Sprague-Dawley or Long-Evans rats wer e surgically prepared with indwelling jugular catheters and 3 days lat er received chronic injections of nicotine (0.4 mg/kg SC) or vehicle ( saline, 1 ml/kg) for 7 days in their home cage. The next day, 2-h dail y test sessions were initiated, during which rats were given the oppor tunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio (FR-1) schedule of rein forcement with a 20-s time out after each infusion. One hole was defin ed as active while pokes in the other hole were recorded but had no sc heduled consequence. The response requirement was increased progressiv ely to five (FR-5) over successive sessions. Both saline- and nicotine -pretreated Sprague-Dawley rats showed a preference for the active hol e, while only the saline-pretreated Long-Evans rats acquired the self- administration as defined by significant differences between respondin g in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed stable levels of maintain ed responding for nicotine, substituting saline for the nicotine or pr etreating with mecamylamine (2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained. These results support previous reports that nicot ine can serve as a reinforcer in rodents and demonstrate that environm ental factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration.