Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Abstract

Recent experiments from our laboratory have demonstrated that drug states can signal when environmental cues will be followed by rewarding outcomes (ie Pavlovian conditioning). However, little is known about the generality of this approach and whether it can be used for studying the pharmacological properties of drug states. Accordingly, the present experiments tested the pharmacological specificity of nicotine (0.4 mg/kg), amphetamine (1 mg/kg), and chlordiazepoxide (CDP, 5 mg/kg) in this Pavlovian drug discrimination procedure. Following drug administration, presentation of a conditional stimulus (CS) was followed by brief access to sucrose. When saline was administered, the same CS was presented but sucrose was withheld. In substitution tests, rats in each condition received varying doses of all training drugs and caffeine. Anticipatory food seeking developed during the CS on drug sessions but not on saline sessions for all drug features (ie drug state-specific conditional response (CR)). In generalization tests, this CR decreased as a function of decreases in the training dose. Median effective doses (ED 50 s) were calculated for nicotine (0.054 mg/kg), amphetamine (0.26 mg/kg), and CDP (2.48 mg/kg). No compound tested substituted for the CDP training drug. Partial substitution was evident between nicotine and amphetamine; CDP did not substitute for either of these drug features. Caffeine fully substituted for nicotine (ED 50 ¼ 15.45 mg/kg) and amphetamine (ED 50 ¼ 3.70 mg/kg), but not for CDP. These results are consistent with the hypothesis that drug states can occasion appetitive Pavlovian CRs in a pharmacologically specific manner.

Characterization of nicotine's ability to serve as a negative feature in a Pavlovian appetitive conditioning task in rats

“…Injection route, as well as injection to placement interval and doses (see later), was based on past nicotine drug discrimination research (cf. Palmatier et al 2005;Stolerman et al 1984;Young and Glennon 2002).…”

“…Maes and Vossen (1997) attempted to establish amphetamine (0.5 mg/kg) or midazolam (0.1 mg/kg) as a negative feature in rats using a goal-tracking task similar to the one described earlier (cf. Palmatier et al 2005). In the Maes and Vossen study, the drug state signaled that 30-s illumination of a light within a food magazine was not followed by a food pellet; in the saline state, the same light CS was followed by food.…”

“…A drug state is a positive feature if it sets the occasion upon which another stimulus (i.e., conditional stimulus or CS) is paired with an unconditioned stimulus (US). We have shown that nicotine serves as a positive feature in an appetitive discrimination task with rats (Palmatier et al , 2005Sanderson et al 2003). In that research, a brief light CS was presented several times in daily 20-min sessions.…”

Pavlovian-Instrumental Transfer of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats

“…Midazolam and amphetamine served as conditional cues that predicted response-independent food delivery signaled by a light. Goal tracking has also been demonstrated with other drug CSs and Pavlovian occasion-setters including cocaine (Troisi & Akins, 2004) and nicotine (Besheer, Palmatier, Metschke, & Bevins, 2004;Bevins, Wilkinson, Palmatier, Siebert, & Wiltgen, 2005;Palmatier, Wilkinson , Metschke, & Bevins, 2004) . So, drug cues can function in a Pavlovian manner in predicting the presence or absence of a US.…”

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

“…For example, repeated pairings of a conditional stimulus such as a chamber or fl avor with a nicotine unconditioned stimulus can produce a place preference (Fudala et al, 1985, Shoaib et al, 1994aand Shoaib et al, 1994b, taste aversion Williamson, 1984 andKumar et al, 1983), or conditioned hyperactivity (Bevins and Palmatier, 2003, Bevins et al, 2001, Shoaib et al, 1994a, Shoaib et al, 1994band Walter and Kuschinsky, 1989 in rats. More recently, systemic nicotine has been found to serve as a positive drug feature (occasion setter) indicating when a discrete light conditional stimulus will be followed by brief access to liquid sucrose and Palmatier et al, 2005. Nicotine can also cue when a discrete light conditional stimulus will not be followed by sucrose, thereby serving as a negative drug feature (Bevins et al, 2006).…”