Methamphetamine and marijuana are drugs that are often abused together. Methamphetamine is a powerful psychostimulant, inducing a pleasurable “rush” in users due to a release of dopamine in the nucleus accumbens (NAcc). The NAcc also has a moderate density of cannabinoid receptors, which are stimulated by marijuana use, suggesting that the NAcc is involved with cannabis dependence as well. It was the goal of this study to determine if an interaction exists between methamphetamine and cannabis, and if the NAcc is the site of this interaction. Adult male Sprague-Dawley rats (300-325g) were trained to selectively press an active lever for food. After training, the rats underwent surgery, in which a cannula guide was inserted into their brains at the level of the NAcc. After seven days of recovery, methamphetamine (10µg/µL) was self-administered into the NAcc via reverse microdialysis. AM 251, a selective CB1 cannabinoid antagonist, or 10% dimethyl sulfoxide was dialyzed directly into the NAcc before all self-...

The ventral tegmental area in the midbrain modulates reward processing. Drugs of abuse can increase midbrain dopamine (DA) activity, and can alter ventral tegmental area glutamate plasticity, leading to addiction. While DA neurons are the principal medi...

As more states accommodate for the legalization of cannabis, the social stigma and perceived harms associated with cannabis use continue to decline. Cannabis use during sensitive developmental periods, particularly during adolescence, has become a major...

CB1 agonists, including delta 9-tetrahydrocannabinol (the main psychoactive ingredient in marijuana), have been shown to increase feeding in rats and humans. Conversely, it has been reported that acute administration of CB1 antagonists reduces food intake in rats. Based upon this observation, it has been suggested that CB1 antagonists could be useful as appetite suppressant drugs. The present studies were designed to provide a detailed examination of the effects of CB1 antagonists on food intake across a broad range of paradigms. Two CB1 antagonists (AM 251 and SR 141716A) were administered to rats trained on two food-reinforced operant schedules (fixed ratio 1 and fixed ratio 5). Both drugs produced a dose-dependent decrease in lever pressing, with little evidence of motor slowing as defined by analyses of the interresponse time distributions. To characterize further the putative appetite suppression produced by these compounds, the effects of AM251 and SR141716A on feeding behavior were assessed using di...

The type three serotonin (5-HT3) receptor is the only ion channel receptor for serotonin. This receptor modulates visceral afferent information and visceral reflexes, participates in nociception, cognition, and has been suggested to play a role in the biology of drugs of abuse. The central CB1 cannabinoid receptor is a G-protein-coupled receptor that mediates the effects of the major psychoactive constituent of marijuana, delta 9-tetrahydrocannabinol. In recent studies, we demonstrated that 5-HT3 and CB1 receptors are co-expressed in many neurons throughout the central nervous system (CNS) (Morales and Backman, 2002; Morales et al., 2002). Experimental animal studies and clinical observations indicate that antagonists of the 5-HT3 receptor and agonists of the CB1 receptor have analgesic and antiemetic properties, suggesting overlap of these receptors at the functional level. As 5-HT3 and CB1 receptors are expressed in the peripheral nervous system (PNS), we investigated whether they coexist in neurons of t...

C. Roe, C. Allen & R. Mason* School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, England. Recent evidence supports the existence of a novel CB receptor in addition to CB1 receptors expressed in the hippocampus. The effects of the CB1/2 receptor agonists Δ-9-THC, CP55940, WIN55,212-2 and HU-210 were examined on firing activity of rat hippocampal neurones under different anaesthetic regimens. Multiple single-unit extracellular activity was recorded from hippocampal CA1 & CA3 neurones in adult male Sprague-Dawley rats under urethane, halothane-N2O:O2 or isoflurane-N2O:O2 anaesthesia with multi-channel microwire electrode arrays (NBLabs, Tx) via a Plexon MAP system. Cannabinoid agonists (0.05-1mg.kg-1), the CB1 antagonist SR171614A (0.1mg.kg-1) or vehicle were administered i.v. CB1 agonists produced a dose-dependent inhibition of firing in the majority of neurones recorded with a rank order WIN55,212-2 = CP55940 > Δ-9- THC; some neurones were either activated (∽20%) or u...

Tau-associated filamentous aggregates are neuropathological hallmarks of Alzheimer’s disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), whereas α-synuclein-positive Lewy bodies are features of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Factors underlying the genesis and functional impact of these aggregates remain poorly understood. Protein kinase M zeta (PKMζ), the catalytic fragment of PKCζ, plays a key role in the maintenance of long-term potentiation, a widely studied model of memory and synaptic plasticity (Ling et al. Nat Neurosci 5:295, 2002). We have demonstrated an association of PKMζ and atypical PKCs (ι and ζ) with neurofibrillary tangles and Hirano bodies in AD (Crary et al. Soc Neurosci Abs, 2002). In the present study, we investigated the relationship of atypical PKCs and PKMζ to abnormal inclusions in PiD (n=2); PSP (n=3); CBD (n=3); and DLB with AD (n=3). Immunohistochemical study was performed on autopsy brain t...

Cannabinoid-type 1 receptors (CB1) are highly expressed in the central nervous system where they modulate neurotransmitter release and synaptic plasticity through intracellular signaling. Specifically, CB1 activates the Giβγ subunit, which binds to G pr...

Rationale: Posttraumatic stress disorder (PTSD) lifetime prevalence is estimated to be approximately 7% in USA, with high prevalence rates in victims of interpersonal violence and combat veterans. Evidences based on pharmacological and psychological int...

Recent evidence suggests that endogenous cannabinoids in the CNS inhibit neuronal activity and neurotransmitter release. These effects are mediated by Gi/o coupled CB1 receptors, which are abundantly expressed in cerebellum, hippocampus, cortex and basal ganglia. Additional evidence suggests that CB1 receptor signaling is negatively modulated in a use-dependent fashion. The novel regulators of G protein signaling (RGS) proteins have potent GTPase activating effects at Gi/o subunits and thus could subserve negative feedback of CB1R signaling. We are using several lines of investigation to test this hypothesis. Six hr after an acute injection of THC, or 24 hr after a 15 d regimen of daily THC injections, mice were killed and processed for in situ hybridization to RGS4 mRNA in sections of prefrontal cortex, striatum, and cerebellum. RGS4 mRNA levels were increased in entorhinal cortex and hippocampus with a trend towards increased expression in striatum, but not in thalamus, 6 hr after an acute injection of T...