The motivation to obtain nicotine-conditioned reinforcers depends on nicotine dose.

Stimuli associated with nicotine (NIC) can acquire new meaning via Pavlovian conditioning. If a stimulus is associated with the primary reinforcing effects of NIC, the new conditional properties of the stimulus should make it a more valuable reinforcer (i.e., increase the motivation to obtain the stimulus), and this value should be based, in part, on the strength or intensity of the primary reinforcer (i.e., NIC dose). The purpose of the present study was to investigate whether NIC-conditioned reinforcement increased motivation to obtain non-NIC stimuli, as reflected by performance on a progressive ratio (PR) reinforcement schedule, and whether this increased motivation was systematically related to NIC dose. Two Paired groups were allowed to nose-poke for NIC (0.03 or 0.09mg/kg/infusion, IV) accompanied by 15-s illumination of a stimulus light (conditional stimulus or CS). Two Unpaired groups (0.03 or 0.09mg/kg/infusion) could also make a nose-poke response for the CS; however their NIC infusions were controlled by the Paired group (i.e., yoked design). A fifth group (CS-Only) was allowed to nose-poke for CS presentations and saline infusions. After 29 conditioning sessions the nose-poke operant was prevented by obscuring the receptacle and the CS (accompanied by saline infusion for all groups) was made contingent upon a novel operant response (lever press). During the acquisition of this novel response, each CS/saline infusion earned increased the number of responses required to earn the next CS/saline infusion. Pairings with the primary reinforcing effects of NIC resulted the acquisition of a novel response for the CS. Motivation to obtain the CS depended on salience (dose) of the primary reinforcement (NIC).

Nicotine serves as a feature-positive modulator of Pavlovian appetitive conditioning in rats.

The present experiments examined whether a nicotine state could set the occasion for a pairing between visual cues and a rewarding outcome in rats. Following nicotine administration, presentation of a conditional stimulus (CS; light-on) was followed by brief access to a sucrose solution. When saline was administered, the same CS was presented but was not followed by any consequence. In Experiment 1, two groups assessed whether rats could acquire this Pavlovian feature-positive discrimination via different training procedures. An anticipatory food-seeking conditioned response (CR) developed during the CS on nicotine sessions but not on saline sessions in both groups. In Experiment 2, centrally acting antagonists of nicotinic acetylcholine and opiate receptors (mecamylamine and naloxone, respectively) dose-dependently blocked nicotine's control of the CR, whereas the peripherally acting nicotinic antagonist hexamethonium had no effect. Increasing or decreasing the interval between nicotine administration and testing also attenuated the CR. These results are consistent with the hypothesis that nicotine can occasion appetitive Pavlovian relations via its action at central nervous system cholinergic receptors.

Effects of chronic caffeine pre-exposure on conditioned and unconditioned psychomotor activity induced by nicotine and amphetamine in rats.

Three experiments examined the effects of chronic pre-exposure to caffeine on the subsequent conditioned and unconditioned locomotor activating effects of nicotine or amphetamine in rats. Rats were given daily intraperitoneal injections of caffeine anhydrous (0, 10 or 30 mg/kg base) for 30 days. Conditioning (environment-drug pairings) began after the last day of caffeine pre-exposure. Pre-exposure to 30 mg/kg of caffeine enhanced the acute and chronic locomotor effects of amphetamine (0.5 mg/kg). A similar enhancement of activity was not seen with the high (0.421 mg/kg base) or low dose (0.175 mg/kg) of nicotine. In a drug-free test, the distinct environment paired with amphetamine and the high dose of nicotine evoked increases in activity relative to controls. Caffeine pre-exposure did not affect expression of this conditioned hyperactivity. These effects of caffeine pre-exposure on amphetamine-induced activity could not be attributed to non-specific effects of caffeine.

Chronic caffeine exposure in rats blocks a subsequent nicotine-conditioned taste avoidance in a one-bottle, but not a two-bottle test.

Two experiments were conducted in order to investigate nicotine-conditioned taste avoidance (CTA) following chronic preexposure to caffeine. Rats were given daily intraperitoneal injections of caffeine anhydrous (0, 10, or 30 mg/kg) for 10 or 30 days. Training of the nicotine-CTA began after the last day of caffeine preexposure. On five separate occasions access to a saccharin solution was followed immediately by an injection of 1.2 mg/kg nicotine hydrogen tartrate salt or saline. Nicotine-CTA readily developed in saline-preexposed controls. That is, paired rats drank less saccharin solution than unpaired rats after repeated saccharin-nicotine pairings. A similar pattern of nicotine-CTA was found for rats preexposed to 30 mg/kg caffeine for 10 days. Following 10 days of preexposure to 10 mg/kg caffeine, however, CTA did not develop under standard testing conditions. Thirty days of caffeine preexposure did not affect the development of a nicotine-CTA even though the anorexic effects of caffeine were evident after exposure to 30 mg/kg for this duration. Thus, caffeine exposure appears to weaken acquisition or expression of the conditioned avoidance properties of nicotine. This effect is sensitive to the dose of caffeine and duration of preexposure. Importantly, the pattern of nicotine-CTA does not appear to be due to nonspecific effects of caffeine.