Rats receiving scheduled daily feedings show behavioral activation associated with feeding. This effect was originally attributed to Pavlovian conditioning of food anticipation to a particular time of day, produced by repeated pairings of food and time cues. Later work showed a limitation on conditioned anticipation of regular meals to approximately a circadian interval, suggesting that a circadian oscillator underlies the conditioning. The most recent work suggests that this circadian oscillator can be conditioned by a single experience. Rats chronically exposed to a 34-hour feeding schedule fail to show conditioned anticipation of the 34-hour feeding interval, but do consistently show a burst of activity 24 hours after the meal on the previous day. We propose that this circadian oscillatory system may constitute a basis of internally generated craving (i.e., craving arising in the absence of environmental cues). If aspects of this oscillatory system are entrained by drugs of abuse, this could mediate a circadian fluctuation in drug craving, leading to an increased probability of drug taking or relapse at times of day related to previous drug intake. Given the common role of the mesocorticolimbic dopamine system in motivated behavior, including feeding and sexual behavior, and in the reinforcing properties of drugs of abuse, it is possible that it also plays a role in the entrainment process. In the proposed experiments, the ability of methamphetamine, an abused drug, to entrain behavioral activation will be tested. Additional experiments are proposed to address four questions: 1 ) what is the relationship between this drug-entrainable oscillator (DEO) and known circadian oscillators responsive to feeding (FEO) and light (LEO)? 2) Does the DEO, like the FEO, show entrainment to a single event? 3) Does the DEO, like the FEO, re~merge, after a prolonged quiescence, consistent with a long term liability to facilitate relapse? 4) is there evidence for specific enhanced drug craving during the periods of induced behavioral activation?
| Kosobud, Ann E K; Gillman, Andrea G; Leffel 2nd, Joseph K et al. (2007) Drugs of abuse can entrain circadian rhythms. ScientificWorldJournal 7:203-12 |
| Pecoraro, N; Kosobud, A E; Rebec, G V et al. (2000) Long T methamphetamine schedules produce circadian ensuing drug activity in rats. Physiol Behav 71:95-106 |
| Kosobud, A E; Pecoraro, N C; Rebec, G V et al. (1998) Circadian activity precedes daily methamphetamine injections in the rat. Neurosci Lett 250:99-102 |
