Considerable anecdotal reports suggest that marijuana enhances 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. The taste reactivity (TR) test was used to evaluate the potential of THC to modify sucrose palatability as measured by the frequency of tongue protrusions. On each of the 9 test trials, rats were injected with either THC (0.5 mg/kg) or vehicle 30, 60 or 120 minutes prior to receiving a 5 min intraoral infusion of 2%, 10% and 32% sucrose solution. The TR test revealed that at 120 min post-injection THC increased the palatability of sucrose solution, regardless of the concentration. Current experiments are investigating the effects of THC on quinine palatability using the TR test.

The effects of marijuana and THC on time perception are well documented. Yet, little is known about the mechanisms that underlie these effects. The present series of experiments examined the effects of THC (0.01-5.0 mg/kg) and of the CB-1 antagonist SR-141716 (0.01-3.0 mg/kg) using a 10-14 second temporal response differentiation schedule in male Sprague-Dawley rats. Under this schedule, subjects were required to make a continuous response on an operant lever for at least 10, but not more than 14 seconds. Releasing the lever within this 10-14 second window resulted in food pellet delivery. Failure to release the lever within this 10-14 second window had no programmed consequences. Acute administration of SR-141716 shifted the distribution of response durations to the right, perhaps suggesting a slowing of the internal timer. In a separate experiment, acute administration of THC produced a generalized disruption in task performance but did not systematically alter the distribution of TRD response durations....

Recent reports have shown that Δ9-tetrahydrocannabinol (THC) stimulates locomotor activity at low doses (≤2.0 mg/kg), while higher doses (>2.0 mg/kg) produce decreases in spontaneous activity. Using quantitative [14C]2-deoxyglucose (2-DG) autoradiography we have systematically studied the effects of acute Δ9-tetrahydrocannabinol in these dose ranges on rates of local cerebral glucose utilization. The present series of experiments was designed to determine if THC-mediated changes in cerebral metabolism followed a clear dose-response relationship. Adult male Sprague-Dawley rats were treated with either vehicle or THC (0.25, 1.0, or 2.5 mg/kg, i.p.) and the 2-DG procedure was initiated 15 min following exposure. Administration of 2.5 mg/kg THC produced significant decreases in cerebral metabolism in most brain regions studied. In contrast, administration of the two lower doses (0.25, 1.0 mg/kg) of THC produced more restricted effects on metabolism. Significant decreases in metabolism were limited to anterior ...

Cannabinoids and the endocannabinoid system have attracted considerable interest for therapeutic applications. Nevertheless, the mechanism of action of one of the main nonpsychoactive phytocannabinoids, cannabidiol (CBD), remains elusive despite potentially beneficial properties as an anti-convulsant and neuroprotectant. Here, we characterize the mechanisms by which CBD regulates Ca2+ homeostasis and mediates neuroprotection in neuronal preparations. Imaging studies in hippocampal cultures using fura-2 AM suggested that CBD-mediated Ca2+ regulation is bidirectional, depending on the excitability of cells. Under physiological K+/Ca2+ levels, CBD caused a subtle rise in [Ca2+]i, whereas CBD reduced [Ca2+]i and prevented Ca2+ oscillations under high-excitability conditions (high K+ or exposure to the K+ channel antagonist 4AP). Regulation of [Ca2+]i was not primarily mediated by interactions with ryanodine or IP3 receptors of the endoplasmic reticulum. Instead, dual-calcium imaging experiments with a cytosoli...

Cannabinoids, including cannabidiol (CBD), a non-psychoactive component of cannabis sativa, have been shown to exhibit anticonvulsant properties in animal models of epilepsy (Wallace et al. 2001; 2003). To investigate cannabinoid-mediated seizure control, CBD was compared to the synthetic CB1 receptor agonist HU-210 in a rat model of kainate-induced temporal lobe seizures (TLS) in vivo. Multiple single-unit and local field potentials (LFPs) were recorded from the hippocampus of male Sprague Dawley rats (200-300g) anaesthetised with urethane (1.3g kg-1 i.p.) or isoflurane/N2O/O2 using 16-channel micro-wire electrodes (NB Labs) and a Plexon Map system. Kainate (KA: 10mg kg-1), cannabidiol (10 or 40mg kg-1) or HU-210 (100μg kg-1) were administered i.p. Data was analysed with Neuroexplorer, including firing frequency, burst analysis, T50 for KA-induced effects, and LFP power spectral density (PSD). While CBD reduced basal firing in ∼20% of cells, CBD did not alter KA-induced firing administered before (n=63 ce...

Most studies of human drug abuse highlight dependence on one primary agent without explicitly considering use of other psychoactive agents such as marijuana (MJ). We previously showed regional cerebral dysfunction in methamphetamine (MA) abusers, particularly in limbic/paralimbic areas, and now assess the combined effects of MJ and MA on cerebral function. We studied 14 MA abusers who reported MA as their drug of choice, had on average used MA for >8 years, and used it on most of the 30 days prior to entering the study. We separated this sample into one group of subjects who reported no substantial drug use other than MA abuse (-MJ, n=7), and another group of subjects who either used MJ frequently (>1 joint/wk) or met DSM-IV criteria for THC dependence (+MJ,n=7). Both groups abstained from all illicit drug use for 5–11 days before assay of global and regional cerebral glucose metabolism (CMRglc, rCMRglc) with PET during performance of an attentional task. The +MJ group had 6% lower CMRglc than the -MJ grou...

Rats previously exposed to amphetamine (AMPH) show enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced self-administration of AMPH and cocaine. The present experiments assessed the effects of pre-exposing rats to Δ9-THC. Rats in different groups were given five pre-exposure injections of saline or one of five doses of Δ9-THC (0.4, 0.75, 1.5, 3.0, 6.0 mg/kg, IP), one injection every third day, and tested two to three weeks later. Previous exposure to all but the lowest dose of Δ9-THC enhanced the locomotor response to AMPH (0.75 mg/kg, IP) but all failed to enhance NAcc DA overflow in response to AMPH. Previous exposure to 3.0 mg/kg (IP, the most effective Δ9-THC dose above) also enhanced forskolin-evoked adenylyl cyclase activity in the NAcc and rats’ locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg, SC), suggesting that previous exposure to Δ9-THC enhances locomotor responding to AMPH by up-regulating postsynaptic DA receptor ...

Delta-9-tetrahydrocannabinol (THC) is the most widely abused illicit drug and its reinforcing properties have been demonstrated in animal models. However, the brain regions that are involved in the reinforcing effects of THC have not been identified yet. In the present study we investigated the rewarding and psychomotor stimulant effects of THC in several discrete brain sites. We found that rats would learn to lever-press for microinjections of THC directly into the posterior ventral tegmental area (VTA). Lever-pressing for THC in the posterior VTA was extinguished when vehicle was substituted for the drug, and was reinstated when THC reinforcement was re-established. Rats did not learn to lever-press for microinjections of THC into the anterior VTA or into a region dorsal to the posterior VTA. Injection of THC into the posterior VTA induced a moderate increase in the locomotor activity, while injections into the anterior or dorsal to VTA did not affect locomotion. The effects of THC in the nucleus accumbe...

Abnormalities in executive function and the ability to successfully monitor and inhibit inappropriate behaviors have been reported in substance abusing individuals. Recent investigations which have utilized neuroimaging and neurocognitive techniques to evaluate frontal systems in heavy cannabis smokers have reported alterations during inhibitory tasks which require frontal processing. Diffusion tensor imaging (DTI) methods provide a quantitative estimate of white matter integrity, providing new insight at the microstructural level. We applied diffusion tensor imaging techniques (DTI) and a brief neurocognitive battery which included measures of frontal/executive function to examine the relationship between frontal white matter changes and neuropsychological performance in nine heavy cannabis smokers and 9 matched control subjects. DTI data were acquired on a 3.0 Tesla scanner using a diffusion weighted twice-refocused spin echo EPI sequence. Voxels (11cm3) were placed in the midline of the splenium of the ...

No study regarding effects of Δ9-THC and nicotine co-administration on motor functions is known. Therefore, it was interesting to investigate functional consequences of intracerebellar (ICB) microinfusion of nicotine on ICB Δ9-THC-induced ataxia. Cerebellum was selected because of its established role in Δ9-THC-induced ataxia. Using the Rotorod, the effect of direct ICB microinfusion of various doses of nicotine [5, 2.5,1.25ng] on Δ9-THC [20 µg]-induced ataxia was investigated. There was a significant (p<0.05) attenuation by ICB nicotine on Δ9-THC-induced ataxia in a dose-related manner. The highest nicotine dose (5 ng) virtually abolished the Δ9-THC-induced ataxia. ICB pretreatment with nicotine antagonist hexamethonium (1µg) significantly blocked nicotine’s ability to attenuate Δ9-THC-induced ataxia suggesting that a nicotine - Δ9-THC behavioral interaction involved participation of nAChR. To further elucidate specific subtype of nicotinic receptor involved in the attenuation of Δ9-THC-induced ataxia, di...