Abstract
Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.
Highlights
Cigarette smoking has been conceptualized as a gateway to use and abuse of illicit drugs such as cocaine [1]
Nicotine increases cocaine’s discriminative stimulus and reinforcing effects in rhesus monkeys [10]. In another recent study [4], locomotor sensitization was increased by 98%, conditioned place preference by 78%, and cocaine-induced reduction in long-term potentiation was increased by 24% when nicotine was given prior to, and concurrent with cocaine
Repeated injection of nicotine further increased locomotor activity as compared to acute injection (P < 0.03), results that are indicative of sensitization (Figure 2a)
Summary
Cigarette smoking has been conceptualized as a gateway to use and abuse of illicit drugs such as cocaine [1]. Animal models provide growing evidence for a “priming effect” of nicotine on reward circuitry. This priming effect may increase the risk for cocaine abuse and dependence [3,4]. Animal models of psychostimulant abuse include behavioral sensitization, conditioned place preference, drug discrimination, and self-administration [5]. Nicotine increases cocaine’s discriminative stimulus and reinforcing effects in rhesus monkeys [10] In another recent study [4], locomotor sensitization was increased by 98%, conditioned place preference by 78%, and cocaine-induced reduction in long-term potentiation was increased by 24% when nicotine was given prior to, and concurrent with cocaine.
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