Antidepressant-like effects of Δ9-tetrahydrocannabinol and rimonabant in the olfactory bulbectomised rat model of depression.

The endocannabinoid signalling system is widely accepted to play a role in controlling the affective state. Plant cannabinoids are well known to have behavioural effects in animals and humans and the cannabinoid CB(1) receptor antagonist rimonabant has recently been shown to precipitate depression-like symptoms in clinical trial subjects. The aim of the present study was to investigate the behavioural and neurochemical effects of chronic administration of Δ9-tetrahydrocannabinol (THC) and rimonabant on intact and olfactory bulbectomised (OB) rats used as a model of depression. As expected, OB rats were hyperactive in the open field. Repeated THC (2 mg/kg, i.p. once every 48 h for 21 days) and rimonabant (5 mg/kg, i.p. once every 48 h for 21 days) reduced this hyperactivity, which is typical of clinically effective antidepressant drugs. In intact animals, chronic THC increased brain derived neurotrophic factor (BDNF) expression levels in the hippocampus and frontal cortex but rimonabant had no effect. Rimonabant increased the levels of phosphorylated extracellular signal regulated kinases (p-ERKs(1/2)) in the hippocampus and prefrontal cortex and THC also increased expression in frontal cortex. OB did not affect BDNF or p-ERK(1/2) expression in the hippocampus or frontal cortex and in, contrast to the intact animals, neither THC nor rimonabant altered expression in the OB rats. These findings indicate antidepressant-like behavioural properties of both THC and rimonabant in OB rats although additional studies are required to clarify the relationship between the chronic effects of cannabinoids in other pre-clinical models and in human depression.

Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory.

AIM OF THE STUDY: Mitragyna speciosa Korth from Rubiaceae family is a tropical plant indigenous to Southeast Asia particularly in Thailand, Peninsular of Malaysia and Indonesia. The leaves have been used by natives for their opium-like effect and cocaine-like stimulant ability to combat fatigue and enhance tolerance to hard work. However there is no scientific information about the effect of mitragynine on the cognitive performances. This study is designed to examine the working memory effects of mitragynine which is extracted from Mitragyna speciosa mature leaves. MATERIALS AND METHODS: The cognitive effect was studied using object location task and the motor activity in open-field test. Mitragynine 5, 10 and 15 mg/kg and were administered by intraperitoneal (IP) for 28 consecutive days and evaluated on day 28 after the last dose treatment. Scopolamine was used as the control positive drug. RESULTS: In this study there is prominent effects on horizontal locomotor activity was observed. Mitragynine significantly reduced locomotor activity in open-field test compared with vehicle. In object location task mitragynine (5, 10 and 15 mg/kg) did not showed any significances discrimination between the object that had changed position than the object that had remain in a constant position. CONCLUSION: Our results suggest that chronic administration of mitragynine can altered the cognitive behavioral function in mice.