Acute and repeated exposure to caffeine: effects on reinstatement of extinguished cocaine-taking behavior in rats

Abstract

Previously, we demonstrated that caffeine dose-dependently reinstated extinguished cocaine-taking behavior in rats. In the present study, we determined whether this effect of caffeine would extinguish with repeated exposures. Rats were first trained to self-administered cocaine intravenously. Once reliable self-administration was obtained, the pumps that delivered cocaine were turned off and the lever-pressing behavior was extinguished. Every 4 days the rats were given an injection of caffeine (20.0 mg/kg) and its ability to reinstate responding was measured. Some rats received each of four exposures to caffeine in the previously cocaine-associated environment. Other rats received the first three exposures to caffeine in the home cage and the last exposure to caffeine in the previously cocaine-associated environment. The results indicated that although caffeine was an effective cue for reinstatement of extinguished cocaine taking, the effect was reduced when repeated exposures occurred in the test environment. In addition, when 4 drug-free days were interspersed between self-administration and reinstatement testing, the caffeine effect was greater than when testing was conducted 1 day following the last self-administration session. Thus, extended withdrawal increases the priming effects of caffeine. The results are discussed in terms of the effectiveness of cue exposure as an adjunct to current therapies for cocaine abuse.

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“…The present data are supported by previous data from this and other laboratories with a variety of different behavioral assays in which caffeine was studied at the moderate dose to enhance, increase or potentiate the effects of cocaine (62)(63)(64)(65). Further evidence for attributing potentiated effects of caffeine on cocaine to caffeine's moderate dose, comes from data which show that low and high doses of caffeine are neuroprotective against cocaine-induced DA-ergic neurotoxicity (66,67).…”

Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value

“…This speculation is supported by two reports in the literature showing that in rats caffeine was able to reinstate extinguished cocaine-taking behavior. However, with repeated administration, the ability of caffeine to reinstate cocaine-associated responding was reduced (Worley et al 1994;Schenk et al 1996). It has also been shown in mice during a single day of extinction that caffeine maintained the cocaine-seeking behavior (Kuzmin et al 1999).…”

“…Moreover, caffeine pre-exposure has been shown to accelerate the acquisition of cocaine selfadministration (Horger et al 1991) and to increase cocaine responding under a fixed ratio schedule . Caffeine can also act as a primer for psychoactive drugs, producing the reinstatement of cocaine-taking behavior (Green and Schenk 2002;Schenk et al 1996;Worley et al 1994).…”

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

“…This hypothesis might seem at odds with the results of several reports that indicate that caffeine can reinstate or prevent the extinction of cocaine-seeking behaviour (Worley et al, 1994;Schenk et al, 1996;Self et al, 1996;Kuzmin et al, 1999;Green and Schenk, 2002;Weerts and Griffiths, 2003). However, these effects of caffeine appear to be due to A 1 rather than A 2A receptor blockade (Kuzmin et al, 1999;Green and Schenk, 2002, Solinas et al, 2002, 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004Quarta et al, 2005Antoniou et al, 2005).…”