Psychopharmacology
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We previously showed that the M1/M4-preferring muscarinic agonist xanomeline can acutely attenuate or eliminate cocaine self-administration in mice. ⋯ In terms of xanomeline's potential for promoting abstinence from cocaine in humans, the findings were mixed. Xanomeline did produce reallocation of behavior from cocaine to food with a robust increase in food reinforcers earned at some cocaine/xanomeline dose combinations. However, effects appeared surmountable, and food-maintained behavior was also decreased at some xanomeline/cocaine dose combinations, suggesting clinical usefulness may be limited. These data nevertheless support the notion that chronic muscarinic receptor stimulation can reduce cocaine self-administration. Future studies should show whether ligands with higher selectivity for M1 or M1/M4 subtypes would be less limited by undesired effects and can achieve higher efficacy.
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The "subjective high" from marijuana ingestion is likely due to Δ(9)-tetrahydrocannabinol (THC) activating the central cannabinoid receptor type 1 (CB1R) of the endocannabinoid signaling system. THC is a weak partial agonist according to in vitro assays, yet THC mimics the behavioral effects induced by more efficacious cannabinergics. This distinction may be important for understanding similarities and differences in the dose-effect spectra produced by marijuana/THC and designer cannabimimetics ("synthetic marijuana"). ⋯ Drug discrimination using different training doses of a high-efficacy, full CB1R agonist differentiated between low- and high-efficacy CB1R agonists.
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Randomized Controlled Trial
A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia.
Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies. ⋯ These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted. Clinical trial registry name and registration number: Iranian registry of clinical trials www.irct.ir , IRCT201107281556N26
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Inactivating dopamine (DA) receptors in the caudate-putamen (CPu) attenuates basal and DA agonist-induced behaviors of adult rats while paradoxically increasing the locomotor activity of preweanling rats. ⋯ These results show that DA receptor inactivation causes dramatically different behavioral effects in preweanling and adult rats, thus providing additional evidence that the D2 receptor system is not functionally mature by the end of the preweanling period.
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Enhancement of the endocannabinoid (EC) system may reduce anticipatory nausea (AN). ⋯ JZL195 reduces AN primarily by acting as a FAAH inhibitor, but MAGL inhibition is also indicated.