Increasing evidence suggests that cannabis exposure during neurodevelopment (i.e., perinatal, adolescent ages) results in persistent alterations in brain circuits underlying neuropsychiatric disorders and leads to an increased risk for certain psychiatr...

Cannabidiol (CBD), a compound phytocannabinoid, has been shown to be a CB1/CB2 receptor agonist and likewise having an inverse agonism of the GPR55 receptor. The role of lysophosphatidylinositol (LPI), endogenous ligand of the GPR55 receptor, on the GAB...

Male rats (n = 9) were trained on the accuracy task (Kubie, et al, Abstracts, Society for Neuroscience, 2003), where rat was rewarded when visiting a target location: a 9 cm diameter unmarked circle in a cylindrical enclosure that had 2 cue-cards (black and white) separated by 90 degrees on the walls. Within 5 min sessions, rats must stand still for 1 sec in the target location in order to receive a reward. We examined the effects of tetrahydrocannabinol (THC) or methylphenidate (MPD) pretreatment on this choice response. Drugs were administered ip in increasing doses 1, 3 and 9 mg/kg/day alternating with saline and each rat received either MPD or THC. Different characteristics were registered – the number of correct choices, number of the rewards, speed and number of walking bouts during the session, median distance to choice center and goal, ratio of events in correct and false goals and others. It was found that methylphenidate slightly improved the accuracy of entering the target location since there w...

The expression of cannabinoid receptor CB1 in distinct neuronal sub-populations of the central nervous system poses the question which neurons mediate the pharmacological effects of cannabinoids in the brain. To start answering this question, the well-known pharmacological actions of delta-9-tetrahydrocannabinol (THC, the primary psychoactive constituent of marijuana) were tested in conventional CB1 knockout mice and in a number of CB1 conditional knockout mouse lines, lacking the expression of the receptor in different neuronal subpopulations. Mutant and wild-type littermates controls were tested in the so-called behavioural “tetrad” battery of pharmacological effects of THC. Results showed that that GABAergic forebrain interneurons are not required for the manifestation of the typical pharmacological/behavioural symptoms produced by THC treatment: hypolocomotion, hypothermia, catalepsy and increase of nociceptive threshold. In order to control for the physiological functionality of CB1 expression in the ...

Cannabidiol (CBD) is being developed for treating severe, orphan, early-onset, treatment‑resistant epilepsy syndromes. We have investigated CBD’s discriminative stimulus in rats trained to discriminate between midazolam and saline, and CBD’s reinforcing...

Chronic and heavy marijuana use in adolescence has been associated with impaired cognitive functions such as learning, memory, attention and decision-making. Recent evidence suggests that other factors could predispose teenagers who use marijuana to cog...

The ability of THC and endocannabinoids to stimulate food intake in rats has been demonstrated in recent studies using both peripheral and central administration and a variety of food types. Potential changes in motivational states have been hypothesized to account for some of the cannabinoid-related effects on ingestion. In addition, interactions between cannabinoid and opioid systems that impact ingestive states appear to exist, with synergistic suppression of intake following concurrent administration of antagonists for both CB1 and opioid receptors. The current set of studies first attempted to manipulate the motivational state of Lewis rats by varying the length of pre-drug exposure (prefeed) to food (chocolate cake batter). Duration of prefeed had a pronounced effect on orally-administered THC's ability to stimulate food intake, particularly in comparison to intake following vehicle. Following establishment of a prefeed paradigm in which THC produced reliable significant increases, the ability of, na...

The involvement of dynorphin on Δ-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin ( Pdyn ) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.

Adaptive behaviours and cognition require accurate processing of the endless barrage of sensory information entering the brain. In particular, the brain must appropriately discern this information to engage in contextually appropriate and adaptive memor...

Working memory is an executive function that orchestrates the use of limited amounts of information, referred to as working memory capacity, in cognitive functions. Cannabis exposure impairs working memory in humans; however, it is unclear whether Cannabis facilitates or impairs rodent working memory and working memory capacity. The conflicting literature in rodent models may be at least partly because of the use of drug exposure paradigms that do not closely mirror patterns of human Cannabis use. Here, we used an incidental memory capacity paradigm where a novelty preference is assessed after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in test variations with sets of identical [identical stimuli test (IST)] and different [different stimuli test (DST)] stimuli (three or six) for low-memory and high-memory loads, respectively. Additionally, we developed a human-machine hybrid behavioral quantification approach which supplements stopwatch-based scoring ...