Nicotine as a signal for the presence or absence of sucrose reward: a Pavlovian drug appetitive conditioning preparation in rats

Rationale. In Pavlovian conditioning research, nicotine is typically conceptualized as the unconditioned stimulus (US) that becomes associated with an exteroceptive conditioned stimulus (CS). This research has not explored the possibility that nicotine can also function as a CS. Objectives. The present research examined whether nicotine served as a CS for the presence (CS+) or absence (CS-) of sucrose and started defining its specificity. Methods and results. Rats trained in the CS+ condition had nicotine (0.4 mg/kg, base) paired intermittently with brief access to sucrose. Intermixed were saline sessions without sucrose. Nicotine acquired the ability to evoke goal tracking. This conditioned response (CR) decreased across extinction sessions. The CR was sensitive to nicotine dose (ED50=0.113 mg/kg) and administration to testing interval; 0-min and 100-min delays produced no CR. The CS properties were specific to nicotine in that amphetamine and bupropion substitution was incomplete. Rats in the CS- condition received similar discrimination training except that sucrose was paired with saline. Nicotine also served as a CS-; the saline state CS+ acquired control of goal tracking. Mecamylamine, but not hexamethonium, blocked nicotine's ability to serve as a CS+ and CS-, indicating a role for central nicotinic acetylcholine receptors. Conclusions. Nicotine served as a signal for the presence or absence of sucrose. The extinction, CS-, and substitution results eliminated a psychomotor stimulant account. The conceptualization of nicotine as a CS suggests novel empirical research in which a drug acquires additional inhibitory and/or excitatory value based on other outcomes present during its effects.