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.

We have recently confirmed an association between the Tau H1 haplotype and clinically defined Parkinson’s Disease (PD) in the Norwegian population. In this further extended case-control series, we present systematic association and linkage disequilibrium analyses using Single Nucleotide Polymorphisms spanning the Tau gene. Strong disequilibrium in PD cases implicates an intragenic region likely to contain variants attributing to increased risk of PD, Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD).

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...

Longitudinal studies of children whose mothers smoked marijuana during their pregnancy suggest a relationship between prenatal exposure to marijuana and deficits in various components of executive function. We have developed a mouse model to examine the effects of in utero exposure to Δ-9-tetrahydrocannabinol (THC) on executive function processes. In the series of experiments reported here, we trained mice on a facilitation task in which one stimulus (the facilitator) provides information about the relationship between another stimulus (the target) and food. In Experiment 1, we found no difference in the rate of acquisition of the facilitation task in mice exposed in utero to vehicle, 5 mg/kg THC, or 10 mg/kg THC. In Experiment 2, we found no differential effect of an acute dose of 1 mg/kg THC on performance on the facilitation trials in mice exposed in utero to vehicle, 5 mg/kg THC, or 10 mg/kg THC. However, the challenge dose did increase responding in the intervals between trials (ITIs) compared to a ve...

Curcumin (Curc) and tetrahydrocurcumin (THC) are both phenolic compounds, exerting antioxidant and anti-inflammatory properties that contribute to neuroprotection, for example, in Alzheimer’s Disease (AD) and in chemoprevention. One inflammatory pathway that has been implicated in both diseases is iNOS which catalyzes the production of nitric oxide (NO). Here we examine the bioavailability and anti-inflammatory effects of Curc and THC with different routes of administration: (gavage, GV; intra-muscular, IM; or intra-peritoneal, IP). Mice were injected IP with LPS (lipopolysaccharide, 0.5 µg/g body weight) or vehicle and iNOS production measured in mouse brain. We administered Curc and THC by GV, IP and IM (0.4, 0.4,and 0.2µmoles, respectively) to C57bl mice with or without LPS and collected their plasma and brain. IM-injected Curc and THC resulted in their elevation in plasma and brain by HPLC detection,and significantly reduced CNS iNOS production by Western. Two-step QPCR studies of mouse brain tissue al...

Transient receptor potential V2 (TRPV2) has been proposed to be a high-threshold thermosensor. However, further elucidation of the channel properties and physiological role of TRPV2 have been hindered by the lack of selective pharmacological tools as well as by the species-dependent differences in the activation of this channel. In the present study, we have used cell-based calcium mobilization and electrophysiological assays to identify and characterize several novel cannabinoid TRPV2 agonists. Among these, cannabidiol was found to be the most robust and potent (EC50 = 3.7 μm), followed by Δ9-tetrahydrocannabinol (EC50 = 14 μm) and cannabinol (EC50 = 77.7 μm). We also demonstrated that cannabidiol evoked a concentration-dependent release of calcitonin gene-related peptide (CGRP) from cultured rat dorsal root ganglion neurons in a cannabinoid receptor- and TRPV1-independent manner. Moreover, the cannabidiol-evoked CGRP release depended on extracellular calcium and was blocked by the nonselective TRP channe...

Epilepsy is a common neurological condition affecting 1% of all Americans. Approximately 30% of epileptic patients are refractory to conventional antiepileptic drug treatments. For these patients, the development of new antiepileptic compounds as primary or adjunct therapies is of great importance. Previous data suggests that cannabinoid and cannabimimetic compounds may be of therapeutic utility in the treatment of epilepsy. In the brain, cannabinoids are thought to work primarily via the CB1 receptor. Activation of cannabinoid receptors has a modulatory effect on many ion channels that influence neuronal action potential spike frequency. In vitro data from our lab and others support the hypothesis that activation of CB1 receptors serves to decrease neuronal excitability. However, there is no evidence that CB1 receptors play a role in the anticonvulsant properties of Δ 9-THC in vivo. Using the Maximal Electroshock Model (MES) of seizure in male CF-1 mice with hind limb tonic extension as the test endpoint,...