Enhancement of conditioned preference for a place paired with amphetamine produced by blocking the association between place and amphetamine-induced sickness

Abstract

Rats learn to prefer a place that has been paired with the rewarding effect of amphetamine. Since amphetamine is also known to produce an aversive effect, called here sickness, pairings of a place with amphetamine should produce a place-sickness association as well as the place-reward association that underlies the conditioned place preference. The purpose of the present experiments was to enhance the conditioned place preference produced by place-amphetamine pairings by blocking the place-sickness association. In Experiments 1 and 2, the taste of saccharin was paired with sickness induced by amphetamine or by lithium, respectively. The saccharin taste was presented prior to each pairing of a white chamber with amphetamine to block the place-sickness association. In Experiment 3, a brief placement in a distinctive cage that had previously been paired with lithium-induced sickness preceded each pairing of the white chamber with amphetamine. Blocking of the place-sickness association occurred as evidenced by the reliable enhancement of conditioned place preference obtained in each of the three experiments.

Sensitization of Psychomotor Stimulation and Conditioned Reward in Mice: Differential Modulation by Contextual Learning

“…This is surprising because the rewarding effects of amphetamine show sensitization with repeated treatment as indicated by the acquisition of a drug self-administration habit (Piazza et al, 1989;Horger et al, 1992), responding under a progressive ratio schedule of reinforcement (Mendrek et al, 1998;Vezina et al, 2002) and the development of conditioned place preference (Lett, 1988). Taylor and Horger (1999) reported that animals sensitized to cocaine showed potentiated responding on the CR lever relative to control animals, and this finding is consistent with an earlier report showing potentiated lever responding by amphetamine in animals pretreated with morphine (Cunningham and Kelley, 1992).…”

Susceptibility to conditioned place preference induced by addictive drugs in mice of the C57BL/6 and DBA/2 inbred strains

“…Moreover, it has been demonstrated that blocking aversive association enhances amphetamine-induced CPP (Lett 1988) and that low doses of amphetamine induce place avoidance in an outbred strain of mice (Cabib et al 1996). These observations support the view that aversive and positive effects of amphetamine in CPP interact in algebraic summation, leading to the suppression of the weaker effect.…”

Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus

“…Nevertheless, the psychostimulant (Le Magnen 1969;Reicher and Holman 1977;Carr and White 1986), as a variety of other reinforcing drugs (see Goudie 1979, for review), promotes CTA and a number of results point to CTA as an index of the aversive effects of drugs (Stolerman and D'Mello 1978;Lett 1988) rather than the result of reinforcing-unrelated effects such as conditioned anorexia (Carey 1978).…”

“…However, addictive substances also have well known aversive properties. Dysphoria as well as euphoria is reported by drug users (Resnick et al 1977;Meyer and Mirin 1979;Mello 1983) and animals may avoid flavours previously paired with drug of abuse (Le Magnen 1969;Reicher and Holman 1977;Goudie 1979;Carr and White 1986;Lett 1988).…”

“…Moreover, there is indication that aversive effects of amphetamine may indeed affect the extent of place preference induced by the drug (Lett 1988). Thus, it was suggested that the aversive effects of amphetamine can summate algebraically with its rewarding effects (White et al 1991) and that the final affective response can be determined by the relative weight of each effect.…”