Nicotine-induced conditioning place preference in low and high nicotine-responder rats.

PASTOR V, ANDRES M AND BERNABEU R

Washington

Congreso; Meeting de la Society for Neuroscience; 2011

Society for Neuroscience

Locomotor horizontal activity is a behavioral index of nicotine effects on the brain. It has been shown that rats with low locomotor responses to an acute injection of cocaine are more susceptible to develop cocaine place conditioning than high responders. However, it is unknown if a preexposure to nicotine can predict rewarding properties of this drug. We designed the present study to determine if individual differences in initial responsiveness to nicotine have any predictive value on nicotine place conditioning in rats. Given that adolescence is a time of unique vulnerability to the effects of nicotine, we investigated the effect of nicotine on locomotor activity and conditioned place preference (CPP) in adolescent male Sprague-Dawley (P30-32) rats. We evaluated rats´ locomotor response to a single injection of nicotine (0.4 mg/kg) and animals were classified in high (HR) or low (LR) nicotine responder rats based on whether their locomotor responses were above or below the median activity level of the subject sample. Then, we trained the animals in the CPP paradigm, in order to evaluate nicotine rewarding properties in these two behavioral groups. Following a pretest to determine initial side preference, animals underwent 2, 8 or 14 days of conditioning sessions, with injections of nicotine (0.4 mg/kg) and saline (1 ml/kg) paired with distinct sides of the conditioning apparatus over alternating days. Control animals received saline injections on both sides. A test was conducted 24 h after the conditioning to assess nicotine place conditioning in LR and HR rats. In addition, locomotor activity in the CPP apparatus was measured during pretest, conditioning and test, in LR and HR during the CPP protocol. Our results show that the animals differed in their locomotor response to a single injection of nicotine, with some exhibiting a significant greater response than others (high and low nicotine responders). HR and LR developed CPP with the same strength in a one or a four-trial CPP. Interestingly, in the seven-trial CPP, LR showed a higher CPP score than HR indicating that LR rats may be more susceptible to nicotine rewarding effects than HR. Our findings also emphasize the fact that using animal models based on differential individual responsiveness to drugs may be an effective strategy for identifying genes and cellular mechanisms that can contribute to vulnerability to drug addiction.