The CB1 receptor is found in abundance in the hippocampus, a brain region implicated in learning and memory. Although cannabinoid ligands alter cognition and prevent long-term potentiation (LTP), the CB1-mediated influence of Δ9-Tetrahydrocannabinol (TH...

Cannabinoid drugs exert their pharmacological effects through the activation of the endocannabinoid system. Using phospho-specific antibodies, we have recently described the activation of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (PKB/A...

Delta 9-tetrahydrocannabinol (Δ9-THC) is the active chemical in cannabis. To better understand the central effects of Δ9-THC, we sought to identify brain areas and neuronal populations responsive to acute and chronic administration of different doses of Δ9-THC. We used c-Fos positive immunoreactivity as a marker for Δ9-THC-responsive neurons. Acute Δ9-THC treatment. Rats were habituated to vehicle injections for 2 weeks, and killed two hours after receiving an IP injection on the 15th day of either vehicle or Δ9-THC (5 or 10 mg/kg). Brains were processed for immuno-detection of c-Fos. Δ9-THC induced c-Fos expression in the central nucleus of the amygdala (CNA). All rats treated with 10 mg/kg showed high levels of c-Fos expression, the lower dose (5 mg/kg) induced variability of c-Fos expression in the CAN. These results may indicate variability in the rat population in response to low doses of acute Δ9-THC. Chronic Δ9-THC treatment. Rats were injected for 2 weeks with daily single injections of 5 or 10 mg/...

Anecdotal reports suggest that cannabinoid agonists enhance palatability and antagonists reduce palatability; however there has been little direct experimental evidence for these claims. The taste reactivity (TR) test is a direct measure of palatability in rats. In Experiments 1 and 2, the taste reactivity (TR) test was used to evaluate the potential of delta-9-tetrahydrocannabinol (THC) to modify both sucrose and quinine palatability. The TR test revealed that THC increases the palatability of sucrose solutions at 120 min post-injection, regardless of the concentration. THC also decreased the aversiveness of the quinine solution regardless of the post-injection interval. In Experiment 3, the taste reactivity (TR) test was used to evaluate the potential of AM251 to modify both sucrose and quinine palatability. The TR test revealed that AM251 decreased the palatability of sucrose regardless of the post-injection interval. Surprisingly, AM251 had no effect on quinine palatability.

Cannabis use has been associated with deficits in prefrontal-dependent cognitive processes in humans. We therefore sought to investigate whether THC administration would produce attentional set-shifting deficits in the rat, using a task (Birrell, J.M. and Brown, V.J. J. Neurosci. 2000, 20, 4320-4324) that enables assessment of comparable cognitive processes. In addition, in situ hybridisation was employed to investigate coincident alterations in the expression of neural activation markers in order to elucidate the neural substrates that may underlie the observed behavioural deficits. 30 minutes prior to behavioural testing, male hooded Long-Evans rats were administered vehicle, 0.01 or 1.0 mg/kg THC i.p. Administration of the higher dose of 1.0 mg/kg THC induced deficits in reversal learning (p < 0.05 at all 3 reversal stages), and the ability to shift attention within a perceptual dimension (intradimensional shift, IDS) (p < 0.05). Analysis of IEG mRNA expression showed that whilst THC–induced deficits in...

Recently our lab demonstrated that delta-9-tetrahydrocannabinol (THC) was more potent or efficacious producing antinociception and catalepsy in female rats than in male rats. The purpose of this study was to determine if sex differences in THC-induced antinociception or catalepsy are due to sex differences in the contribution of supraspinal versus spinal cannabinoid receptor 1 (CB1) activation. SR141716A, a selective CB1 receptor antagonist, or vehicle was administered i.c.v. or i.t.; the time course of SR141716A antagonism of 10 mg/kg i.p. THC or vehicle-induced antinociception (paw pressure test) and catalepsy (bar test) were determined. Baseline antinociceptive and cataleptic scores were similar between the sexes in all groups. THC alone produced similar antinociception in males and females but produced greater catalepsy in females. SR141716A alone did not produce any significant effects. I.c.v. SR141716A did not significantly antagonize systemic THC-induced antinociception, but significantly antagonize...

Marijuana shares similar properties with ethanol, nicotine and phencyclidine, drugs which can produce addiction in humans, but generally do not elicit reward behavior in animals. Marijuana often elicits conditioned place aversion in animals. Also, the effect of stress on marijuana use/abuse is an area that is virtually ignored. In our experiments, development of marijuana place preference to dose-time response variations, amphetamine (amp) sensitization and different stressors (isolation, swimming, restraint) was examined. Preconditioning preferences of Wistar rats were determined in a 3-chambered box, with black and white compartments (30x 30x 15) separated by a central neutral compartment (15x 30x 15). Increased spontaneous motor activity (SMA)determined the dose of marijuana that was stimulatory (CS) and the duration of the response. Rats were treated i.p. with CS or saline and subjected to an 8-day place preference-conditioning paradigm, with confinement times of either 18 min (6 rats) or 40 min (6 rat...

Chronic administration of Δ9-THC (THC), a partial agonist for cannabinoid (CB1) receptor activation of G-proteins, produces dramatic desensitization of CB1 receptors throughout the brain. These studies were conducted to compare the effects of THC treatment with those produced by WIN 55,212-2 (WIN), a full agonist for CB1-mediated G-protein activation in brain. Mice were treated twice daily (s.c.) for 15 days with escalating doses of WIN (3-48 mg/kg), THC (10-160 mg/kg) or vehicle. Animals were either examined for tolerance in behavioral assays or brains were collected and processed for CB1-stimulated [35S]GTPγS autoradiography. Chronic treatment with either WIN or THC produced tolerance to CB1-mediated effects on spontaneous activity, hypothermia and antinociception. Densitometric analysis revealed decreased CB1-stimulated [35S]GTPγS binding in all regions examined in THC- and WIN-treated brains. CB1-stimulated G-protein activity in THC-treated animals was generally lower than in WIN-treated animals, altho...

The endocannabinoid system exerts multiple and complex modulatory physiological functions. For instance, accumulative evidence has suggested that the endocannabinoid system modulates the sleep-wake cycle. Among the elements of the endocannabinoid system...

Epilepsies are neurological disorders characterized by the presence of epileptic seizures and neuropsychiatric comorbidities. The Wistar Audiogenic Rat (WAR) is a rodent strain capable of developing epileptic seizures in response to intense sound stimul...