Effect of chronic nicotine on brain stimulation reward. I. Effect of daily injections.

Previous work has shown that nicotine facilitates brain stimulation reward (BSR) but that the maximum effect obtainable with nicotine is similar to that seen with nonaddictive compounds. This study examined whether repeated nicotine injections would enhance the facilitatory action of nicotine on BSR. Rats with lateral hypothalamic stimulating electrodes were tested using a threshold-tracking procedure. This procedure determined the minimum stimulation frequency (i.e. stimulation threshold) necessary to maintain 30 presses/min during 30-min test sessions. Rats were injected daily with nicotine bitartrate (0.5 mg/kg, s.c., dose expressed as free base weight) or physiological saline (1 ml/kg, s.c.) immediately before testing for 21 consecutive days. Nicotine lowered thresholds across the 21-day injection regimen. Neither tolerance nor sensitization to this effect was apparent. The magnitude of threshold lowering produced by nicotine was similar to that previously reported for acute nicotine and for mild stimulants with low addiction liabilities (i.e. caffeine and pseudoephedrine). This finding suggests that even under chronic administration, nicotine's profile in this animal model is that of a substance with a low addiction liability.