The VTA is necessary for reward behavior with dopamine cells critically involved in reward signaling. Dopamine cells in turn are innervated and regulated by neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile-adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1). LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates. Bath applied Δ9-tetrahydrocannabinol depressed GABA cell activity, therefore downstream dopamine cells will be disinhibited; and thus, this could potentially result in increased reward. Chronic injections of Δ9-tetrahydrocannabinol occluded LTD compared with vehicle injections; however, a single exposure was insufficient to do so. As synaptic modifications by drugs of abuse are often tied to addiction, these data suggest a possible mechanism for the addictiv...

The cannabis industry in the US has experienced tremendous growth in recent years, in part due to a more permissive regulatory environment. The availability of cannabidiol (CBD) in a variety of commercial products has fueled consumer experimentation as ...

Aims: To test if cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa with anxiolytic properties, could prevent the changes in fear processing induced by severe stress. We also investigated possible mechanisms of this effect. Methods: M...

Adolescence is a period of brain development that often coincides with initiation of drug use, including Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana. This exposure can alter development on a neuronal and molecular leve...

Ventilatory (VE) responses to NaCN injections in the descending aorta of CBD piglets demonstrate plasticity in peripheral chemosensitivity (J.Appl.Physiol. 87:2128-2135, 1999). Further, immunostaining shows an increase in serotonin (5-HT) in the subendothelial and adventitia layers of the same aortic areas after CBD (FASEB J. 15(4):A422, 2001). The present study assesses whether the peripheral chemosensitivity after CBD in the aorta requires 5-HT and if chemosensitivity remains after combined aortic and carotid body denervation (AOD+CBD). In 25 piglets, peripheral chemosensitivity (VE responses) was assessed 3 weeks after carotid and/or aortic, or sham denervation by injections of 6.3 mM NaCN (0.05mg.kg-1) into the jugular vein, common carotid arteries and descending aorta, before (control) and after the IV administration of the 5-HT blockers, metoclopramide (MCP), and methiothepin (MTN). Venous NaCN VE responses did not differ among all groups (p = 0.531) whereas carotid responses were present in SHAM and...

Cannabis contains two compounds that produce opposite effects. Delta-9-tetrahydrocannabiol (THC), the main psychotropic component of cannabis, has been shown to induce anxiety and schizophrenia-like symptoms. In contrast, cannabidiol (CBD), the non-psyc...

Limited therapeutic effects of current Alzheimer treatments highlight the need for new research approaches. The endocannabinoid system plays a role in neuroinflammation and memory formation and therefore addresses major pathological hallmarks of Alzheim...

Cannabis use among adolescents is expected to increase as its use becomes legal in a growing number of states and countries. Despite this growth, little is known about the lasting impact of its chemical constituents on brain development. In this study, ...

Brain aging is accompanied by a number of cellular and molecular changes that may ultimately lead to cognitive deficits. One of these changes is a decline in the activity of the endocannabinoid system characterised by diminished 2-arachidonoylglycerol l...

Marijuana is one of the most widely abused illicit drugs and is known to cause significant cognitive impairments. It has been hypothesized that marijuana may preferentially target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana’s more subtle effects on neural mechanisms subserving cognitive functions. To this end, we examined the effects of different doses and treatment regimens (both acute and chronic) of delta-9-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the mouse dentate gyrus (DG), using the bromodeoxyuridine method (BrdU; 200 mg/kg, i.p; 2 h survival time). Administration of THC produced marked dose- and time-dependent behavioral sedation and catalepsy. The number of BrdU labeled cells was not significantly changed from vehicle contr...