Withdrawal from chronic, intermittent access to a highly palatable food induces depressive-like behavior in compulsive eating rats.

The increased availability of highly palatable foods is a major contributing factor toward the development of compulsive eating in obesity and eating disorders. It has been proposed that compulsive eating may develop as a form of self-medication to alleviate the negative emotional state associated with withdrawal from highly palatable foods. This study was aimed at determining whether withdrawal from chronic, intermittent access to a highly palatable food was responsible for the emergence of depressive-like behavior. For this purpose, a group of male Wistar rats was provided a regular chow diet 7 days a week (Chow/Chow), whereas a second group of rats was provided chow for 5 days a week, followed by a 2-day access to a highly palatable sucrose diet (Chow/Palatable). Following 7 weeks of diet alternation, depressive-like behavior was assessed during withdrawal from the highly palatable diet and following renewed access to it, using the forced swim test, the sucrose consumption test, and the intracranial self-stimulation threshold procedure. It was found that Chow/Palatable rats withdrawn from the highly palatable diet showed increased immobility time in the forced swim test and decreased sucrose intake in the sucrose consumption test compared with the control Chow/Chow rats. Interestingly, the increased immobility in the forced swim test was abolished by renewing access to the highly palatable diet. No changes were observed in the intracranial self-stimulation threshold procedure. These results validate the hypothesis that withdrawal from highly palatable food is responsible for the emergence of depressive-like behavior, and they also show that compulsive eating relieves the withdrawal-induced negative emotional state.

The efficacy of mirtazapine in the treatment of cocaine dependence with comorbid depression.

BACKGROUND: Prior findings concerning the use of mirtazapine in the treatment of a variety of substance use disorders and its antagonistic actions at the serotonin 5-HT(2A) receptor suggest that this drug may have efficacy in the treatment of cocaine dependence in the presence of a depressive disorder. METHODS: Depressed cocaine-dependent subjects received either mirtazapine (target dose 45 mg daily) or placebo for 12 weeks. Urine concentrations of benzoylecgonine and self-report were used to assess cocaine consumption. Depression and sleep quality were evaluated using the Hamilton Depression Rating Scale (HAM-D) and the Pittsburgh Sleep Quality Index, respectively. RESULTS: Cocaine consumption during the treatment period did not differ significantly between the mirtazapine (n = 11) and placebo (n = 13) groups in this study. In week 4 sleep latency was significantly lower in the active medication than in the placebo group. Positive effects of mirtazapine treatment on early insomnia were suggested by an item analysis of the HAM-D. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The results of this study suggest that mirtazapine is superior to placebo in improving sleep in patients with comorbid depression and cocaine dependence, but is not more effective than placebo in reducing cocaine use.

Medial forebrain stimulation enhances intracranial nociception and attenuates morphine analgesia suggesting the existence of an endogenous opioid antagonist.

The purpose of this experiment was to test in the rat the hypotheses that activation of the brain reward system would attenuate the effects of intracranial nociceptive stimulation and would potentiate the antinociceptive effects of morphine. In this experiment pain (nociception) was generated by electrical stimulation of a brain pain pathway, the mesencephalic reticular formation (MRF) of the rat. Reward pathway stimulation was to the medial forebrain bundle at the level of the lateral hypothalamus (MFB-LH). Current thresholds for escape from MRF stimulation were determined using a modification of the psychophysical methods of limits. MRF stimulation was delivered concurrently with different intensities of non-contingent MFB-LH stimulation. The effects of morphine and saline were determined under all stimulation conditions. Contrary to expectation MFB-LH stimulation significantly lowered MRF stimulation escape thresholds. Morphine administration elevated MRF thresholds in the absence of MFB-LH stimulation. However, this effect was blocked by concurrent MFB-LH stimulation. These findings, which mimic the effects of the opiate antagonist naloxone, i.e., potentiating of pain and antagonism of morphine's analgesic effects, suggest the presence of an endogenous opiate receptor antagonist.

Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats.

Recent studies have shown that deep brain stimulation (DBS) of the nucleus accumbens (NAcc) has an inhibitory effect on drug-seeking behaviors including reinstatement responding for cocaine. The objective of the present study was to expand on these findings by assessing the effects of DBS on behaviors related to alcohol consumption. The specific aim of this study was to determine whether DBS delivered to either the shell or core of the NAcc would reduce ETOH intake in rats using a two-bottle choice limited access procedure. Long Evans rats were induced to drink a 10% ethanol solution using a saccharin fading procedure. Bipolar electrodes were implanted bilaterally into either the core or shell of the NAcc. During testing animals received DBS 5 min prior to and during a 30-minute test session in which both ETOH and water bottles were accessible. Current was delivered at amplitudes ranging from 0 to 150 microA. ETOH consumption was significantly reduced from baseline levels at the 150 microA current for both shell and core electrode placements. A significant current effect was not found for water consumption for either site. These results provide evidence that DBS delivered either to the nucleus accumbens core or shell subregions can significantly reduce ethanol intake in the rat.