Psychostimulants as well as cannabinoids have been shown to affect a great variety of behaviors in both, humans and laboratory animals, in a serious manner. Our previous studies repeatedly demonstrated that control groups with saline injection(s) have d...

Marijuana is the most widely used illicit substance in the USA, and there is no effective medication available to treat marijuana abuse. Delta-9-tetrahydrocannabinol (THC), the active constituent in marijuana, significantly stimulates the brain mesolimbic dopamine (DA) system and enhances brain stimulation reward. We have previously shown that blockade of brain DA D3 receptors by SB-277011A significantly attenuates cocaine- or nicotine-enhanced brain reward, cocaine self-administration, cocaine- or heroin-conditioned place preference, and cocaine- or nicotine-induced reinstatement of drug-seeking behavior (Heidbreder, et al, 2005). In the present study, we investigated whether SB-277011A inhibits THC-enhanced brain stimulation reward and THC-induced increase in DA in the nucleus accumbens. THC (0.25 mg/kg i.p.) reliably shifted brain-reward stimulation curves to the left, lowering stimulation thresholds by around 15% in male Lewis rats. SB-277011A (3-12 mg/kg i.p., 1 hour prior to THC) dose-dependently blo...

Cannabis abuse during adolescence is a risk factor for cognitive impairments in psychiatric disorders later in life (Renard et al., 2016). Specifically, early exposure to Δ9-tetrahydrocannabinol (THC; i.e. the main psychotropic component of cannabis) ca...

Despite increased prevalence of maternal cannabis use, little is understood regarding potential long-term effects of prenatal cannabis exposure (PCE) on neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases the risk of developing affective/mood disorders in adulthood, the precise neuropathophysiological mechanisms in male and female offspring are largely unknown. Given the interconnectivity of the endocannabinoid (ECb) system and the brain’s fatty acid pathways, we hypothesized that prenatal exposure to Δ9-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through alterations of fatty-acid dependent synaptic and neuronal function in the mesolimbic system. To investigate this, pregnant Wistar rats were exposed to vehicle or THC (3 mg/kg) from gestational day (GD)7 until GD22. Anxiety-like, depressive-like, and reward-seeking behavior, electrophysiology, and molecular assays were performed on adult male/female offspring. Imaging of fatty acids using matrix-assisted ...

Phytocannabinoid derivatives of Cannabis Sativa are an exciting new class of anticonvulsants and one, cannabidiol (CBD), has displayed potent anticonvulsant properties in recent clinical trials in patients with two forms of childhood onset epilepsy. Her...

Glutamatergic plasticity in the nucleus accumbens (NAc) is a key neuronal substrate of appetitive learning that allows adaptive behavioral responding to changing environmental contingencies. Consequently, dysfunction in the expression of synaptic plasti...

Emotional and cognitive disorders often accompany chronic pain. In the general population, chronic pain incidence is 6% to 8%, and its impact on the quality of life, mood, and sleep exceeds the burden of its causal pathology. Considering the nociceptive...

The observation that the psychoactive ingredient of marijuana, delta-9-tetrahydrocannabinol (THC), precipitates psychotic episodes in vulnerable subjects and causes perceptual alterations similar to those observed in schizophrenic patients, suggests tha...

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. l-Theanine is an amino acid analog of l-glutamate and l-glutamine derived from various plant sources, including green tea leaves. l-Theanine has previously been shown to modulate levels of GABA, DA, and glutamate in various neural regions and to possess neuroprotective properties. Using a preclinical model of adolescent THC exp...

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...