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Wheel running activity can shorten the period (tau) of circadian rhythms in rats and mice. The role of serotonin (5HT), in this effect of behavior on circadian pacemaker function, was assessed by measuring tau during wheel-open and wheel-locked conditions in mice sustaining neurotoxic 5HT lesions directed at the suprachiasmatic nucleus (SCN). Intact mice exhibited a significant lengthening of tau (approximately 10 min) within 3 weeks when running wheels were locked. Mice with immunocytochemically confirmed 5HT depletion showed significantly longer tau than intact mice during wheel access, and did not show a significant change in tau up to 6 weeks after wheels were locked. In these mice, variability of tau across wheel access conditions was similar in magnitude to tau variability in intact mice at two time points without wheel access (+/- 3 min). 5HT-depleted mice also exhibited significantly longer activity periods (alpha), and a significantly delayed peak of activity within alpha. Previous studies show that a delayed peak of activity within alpha is associated with longer tau. Group differences in tau, and apparent failure of wheel-locking to lengthen tau in mice with 5HT lesions, may thus be due to loss of a serotonergic behavioral input pathway to the SCN, or to a lesion-induced change in the waveform of the activity rhythm.

We previously reported that systemic or central amygdala injections of the mGluR(2/3) agonist LY379268 (which decreases glutamate release) prevented enhanced cue-induced cocaine seeking in extinction tests after prolonged withdrawal (incubation of cocaine craving). Here, we report that systemic and central amygdala injections of LY379268 also prevented the enhanced cue-induced sucrose seeking in extinction tests after prolonged sucrose-free period (incubation of sucrose craving). These findings suggest that central amygdala glutamate plays an important role in the incubation of reward craving after withdrawal from both drug and non-drug rewards.

We recently reported that systemic injections of the mGluR(2/3) agonist LY379268, which decreases evoked glutamate release, attenuate context- and discrete cue-induced reinstatement of heroin seeking, but not heroin self-administration. Here, we report that systemic injections of LY379268 attenuate context- and discrete cue-induced reinstatement of sucrose seeking, but not sucrose self-administration. These results suggest that similar neuronal mechanisms mediate cue-induced relapse to opiate- and palatable food seeking.

Drugs of abuse, such as amphetamine and morphine, produce reward-related shifts on intracranial self-stimulation (ICSS) thresholds. The facilitatory effects on ICSS thresholds of drugs that act through the GABAergic system, however, are reported to be attributed to their antiseizure and anticonvulsant effects, rather than their reinforcing effects. Using a rate-frequency ICSS paradigm, we examined the effects of amphetamine (a reinforcing drug of abuse that acts via the catecholaminergic system), pentobarbital (a GABA(A) receptor agonist and reinforcing barbiturate with anticonvulsant properties), and gabapentin (a nonspecific GABAergic agonist and anticonvulsant with low abuse potential) on ICSS M(50) indices. All three doses of amphetamine (0.5, 1.0, and 2.0 mg/kg) and pentobarbital (2.5, 5.0, and 10.0 mg/kg) significantly lowered rate-frequency M(50) values. Gabapentin, on the other hand, significantly raised rate-frequency M(50) values, albeit only at the highest dose administered (30 mg/kg). Our results indicate that shifts in ICSS M(50) values produced by pentobarbital are associated with the reinforcing, not the anticonvulsant, effect of pentobarbital. These results are consistent with the view that there is a common system underlying the reinforcing effects of drugs and ICSS reinforcement, and suggest that the reinforcing and anticonvulsant effects of GABA agonists are dissociable.