ensity measured with CP55,940. They proposed that fluoxetine enhanced WIN55212-2 signaling through Gai2 and Gai3 subunits and not through Gao subunits. Treatment with the TCA desipramine increased CB1 binding density in the hippocampus and hypothalamus, without significantly altering AEA or 2-AG levels in rat brains. The CUS protocol altered CB1 density in rat brains, and these changes were attenuated by concurrent treatment with imipramine. Desipramine-induced weight gain was reduced by cotreatment with SR141716A, suggesting an eCB pathway. Treatment with the MAOI tranylcypromine increased CB1 binding density in the prefrontal cortex and hippocampus, and increased 2-AG but decreased AEA levels in the prefrontal cortex. Repeated electroconvulsive shock treatment for depression produced complex and regionally specific effects. Generally EST downregulated CB1 binding density and AEA levels in the cortex, but enhanced cannabinoid-stimulated GTPcS binding in the amygdala. In summary, the effects of antidepressant drugs or treatments upon the eCB system are not definitive, but likely result in CB1 upregulation, at least in some brain regions. Preclinical PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19630074 studies suggest agonist trafficking may be responsible for variable responses. Antipsychotic drugs. First-generation antipsychotic drugs, such as haloperidol and chlorpromazine, are dopamine D2 receptor inverse agonist. Second-generation “atypical”antipsychotics antagonize D2 and 5-HT2A, and also target other neuroreceptors. Acute administration of chlorpromazine enhanced the hypothermic response to THC. Subchronic administration of haloperidol increased CB1 density in rat brains, indicated by Systematic Review of eCB Modulation species, exercise rats administered leptin rats fasted mice fasted goldfish fasted rats after gastric bypass PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19631915 Zucker obese rats fasted doi:10.1371/journal.pone.0089566.t002 measure leptin decreases hypothalamic AEA and 2-AG levels fasting for 24 h increased AEA and 2-AG in limbic forebrain and 2-AG in hypothalamus; reference time-dependent effects: short-term fasting increased hypothalamic 2-AG; long-term fasting decreased hypothalamic 2-AG food K-858 chemical information restriction decreased CB1 mRNA in the forebrain and increased AEA levels in the telencephalon, two effects reversed by refeeding weight loss after Roux-en-Y gastric bypass surgery decreased AEA and with no change in 2-AG levels in skeletal muscle fasting decreased CB1 mRNA in brainstem but not in hypothalamic nuclei increased binding of CP55,940 in the substantia nigra.globus pallidus.striatum. Subchronic haloperidol also potentiated CP55,940-stimulated GTPcS binding in the substantia nigra. Sundram et al. confirmed haloperidol’s effects on CP55,940 binding, and obtained similar results with chlorpromazine and olanzapine. In monkeys trained to discriminate THC, haloperidol sensitized the THC discriminative stimulus. Risperidone increased CP55,940 binding in rat brain without altering CB1 mRNA levels. Four weeks of aripiprazole upregulated CB1 in rat frontal cortex. Clozapine decreased CP55,940 binding in rat brain, and attenuated THC-induced disruption of spatial working memory in the rat radial maze task. Several researchers have proposed that CB1 upregulation during antipsychotic drug treatment may explain appetite enhancement, weight gain, and CB1 supersensitivity. D’Souza et al. conducted a double-blind study 
on the effects of adding haloperidol to THC. Compared to THC alone, the combination of drugs significantly worsened