Acute administration of delta9-tetrahydrocannabinol (THC), the psychoactive ingredient of marihuana, produces dose-dependent locomotor effects that are selectively mediated by activation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in motor control brain regions, such as basal ganglia and cerebellum and modulate synapses between cerebellar granule cells (GC) and Purkinje cells. Chronic THC can induce physical dependence that implicates the cerebellum and THC withdrawal syndrome has an important motor component. However, the neurophysiological adaptive mechanisms occuring during chronic THC treatment and withdrawal remain unexplored. We aimed to evaluate the effects of chronic THC administration and withdrawal on GC neuronal activity using calcium imaging techniques. We first examined the effects of acute and chronic THC on spontaneous neuronal activity patterns of cerebellar GCs circuits. In order to evaluate the effects of THC withdrawal syndrome on these activity patterns, the selecti...

The use of medical/recreational marijuana and its legal market size are on the rise worldwide. Medical Marijuana has potential benefits for different diseases, but the lack of biomedical research and its popularity based on anecdotal evidence poses a ri...

Previous reports have shown that both cannabidiol (CBD) and CID16020040 blocks the GPR55-mediated effects of LPI. In addition, the expression of GPR55 mRNA in the basal ganglia (BG) has been described by in situ hybridization, especially in the striatum...

There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5–20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct canna...

Recent evidence suggests that toxin-induced taste avoidance in the non-emetic rat is not mediated by conditioned sickness. However, it is possible that toxin-induced taste avoidance in an emetic species is mediated by conditioned sickness. The present experiments evaluated the potential of the anti-emetic agents, ondansetron (OND) and delta-9-tetrahydrocannabinol (THC) to interfere with lithium (LiCl)-induced taste avoidance in the house musk shrew (Suncus murinus). In Experiment 1, shrews were pretreated with OND (1.5 mg/kg) or Saline 30 min prior to drinking 0.1% saccharin solution then they were injected with LiCl (390 mg/kg) or saline. When assessed by a two-bottle test over a 12 hr period, but not a one bottle test, the shrews displayed a LiCl-induced saccharin avoidance that was prevented by pretreatment with OND. The relatively weak effects may have been due to floor effects in consumption of saccharin solution; therefore a highly preferred 32% sucrose solution was used in another experiment. In Exp...

Anandamide and delta 9-tetrahydrocannabinol (THC) are endogenous and exogenous ligands for cannabinoid (CB) receptors. While most of anandamide and THC actions are thought to be mediated through endogenous cannabinoid type1 (CB1) receptors, there is evidence that some of cannabinoid-induced behaviors are independent of CB1 receptors. Here, we report that both anandamide and THC increased the amplitude of current activated by glycine in Xenopus oocytes expressing human homomeric and heromeric glycine receptors in a concentration-dependent manner over a concentration range from 30 to 3000 nM. The EC50 values of the THC and ANA concentration-response curves were 86 ± 9 nM and 319 ± 10 nM for the α1 subunits; and 73 ± 8 nM and 318 ± 14 nM for the α1β1 subunits. ANA and THC did not alter GABAA receptor-mediated responses, suggesting that the potentiation by ANA and THC is specific for the glycine receptors. The maximum potentiation by ANA and THC was observed at the lowest concentration of glycine. With increas...

Marijuana is the most widely used illicit drug among women of reproductive age. Neurocognitive deficits have been reported in children whose mothers used marijuana during pregnancy. Maternal consumption of alcohol during pregnancy has long been known to cause serious developmental deficits depending on the amount and timing of exposure during gestation. Here we report that acute administration of Δ9-tetrahydrocannabinol (THC, 1-10 mg/kg), the principal psychoactive cannabinoid of marijuana, has pro-apoptotic properties in the neonatal rat brain when co-administered with a subtoxic dose of ethanol (1.1 g/kg). THC did not induce neurodegeneration when administered alone. Neuronal degeneration became disseminated and very severe when THC was combined with a mildly intoxicating ethanol dose (1.5 g/kg), with the effect of this drug combination qualitatively and quantitatively resembling the massive apoptotic death observed when administering ethanol alone at much higher doses. THC did not influence plasma ethan...

Cross-interactions between opioid and cannabinoid systems in dependence and reward-related processes have been shown in many studies. We have recently established in mice a model of tolerance and dependence to Δ9-tetrahydrocannabinol (THC) as well as a model of place conditioning to evaluate both rewarding and aversive properties of THC. These two models represent useful tools for the study of the neurobiological basis of THC actions. We have now used these models in three strains of knockout mice lacking either μ, δ or κ opioid receptors, to determine the implication of each opioid receptor in tolerance and dependence to THC as well as in the motivational effects induced by this compound. In each strain of knockout mice, we first studied the rewarding and aversive effects of THC (1 and 5 mg/kg) in the place conditioning paradigm. We then studied the development of tolerance to the antinociceptive, hypothermic, and hypolocomotor effects of THC during chronic treatment (20 mg/kg, twice daily). Finally, THC-...

Delta-9-tetrahydrocannabinol (THC) is the major psychoactive constituent of marijuana and is thought to be responsible for acute and long-term behavioral effects seen in humans potentially through a dysfunction of the frontal cortex. In the rat, acute exposure to THC increases cortical dopamine (DA) turnover and disrupts short-term memory (Neuropsychopharm 16:426-432, 1997). In this current study, we examined the effects of a single dose of THC on midbrain DA neurons in non-human primates using the immediate-early gene, c-fos, as an indicator of the initiation of long-term adaptation brought on by acute activation. Twelve male, adult African green monkeys of St Kitts origin (Cercopithecus aethiops sabaeus) were given a single injection of vehicle or THC, 1.25 mg/kg or 2.5 mg/kg. After 1 hour, the monkeys were overdosed on pentobarbital, perfused with saline, and the brains were placed in 4% formalin for 24 hours. The midbrains were cut into 50 μm sections and stained for Fos-immunoreactivity (Fos-ir) and t...

The prefrontal cortex (PFC) regulates multiple psychological processes including anxiety, sociability, attention, flexibility and cognition. Considerable evidence underscore its critical role in the development of various types of psychiatric disorders ...