The two-hit hypothesis of adult psychopathology predicts that a combination of prenatal and postnatal environmental insults increases risks for major psychiatric disorders. We generated a mouse model of environment x environment (E x E) interaction base...

Epidemiological studies suggest a link between early adolescent cannabis use and risk of developing schizophrenia, but whether Δ9-tetrahydrocannabinol (THC) actually precipitates schizophrenia symptoms remains unclear. Moreover, the neurobiological mech...

Novel synthetic cannabidiol enantiomer modulates δ and β wavelength EEG activityApril Contreras1, William A. Maio2, Dustin J. Hines1, and Rochelle M. Hines11Interdisciplinary Neuroscience PhD Program, Department of Psychological and Brain Sciences,Unive...

Therapeutic hypothermia is well-established as a standard treatment for infants with hypoxic-ischemic encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following hypoxic-ischemic (HI) injury with cannabidiol (CBD) at 0.1 or 1 mg/kg i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 (neonatal phase) to 37 days old (juvenile phase). Placebo or CBD were administered at 0.5, 24 and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing), and two cognitive (novel object recognition and T-maze) tests were conducted 30 days after HI. The extent of brain damage was determined by magnetic resonance imaging, histological evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography and Western blotting. At 37 days, the HI insult produced impairments in all neurobehavioral score (cognitive and s...

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...

Disturbances in emotional processing and salience attribution are core features of schizophrenia and other neuropsychiatric disorders. The ventral hippocampus (VHipp) contains large distributions of cannabinoid CB1 receptors (CB1R) that regulate emotion...

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...

Epilepsy is a chronic disorder characterized by abnormal brain cell activity leading to recurrent, unprovoked seizures. Pharmacological therapies are commonly used for the treatment of epilepsy, although nearly 30% of patients do not respond to current ...

Marijuana is the most widely used illicit drug in the United States. Thus, there is a demand for further research to understand the neurobiological effects of cannabis. Our lab has recently established a rodent model of operant Δ9-tetrahydrocannabinol +...

The abuse of Δ-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of marijuana, is associated with persistent cognitive dysfunction. We therefore studied the effects of chronic administration of THC (10 mg/kg) on cognitive function in the rat. THC administration, twice daily for 14 days, resulted in a persistent attentional impairment that is reminiscent of cognitive deficits observed following excitotoxic lesions of the dorsomedial frontal cortex. Specifically, rats chronically administered THC showed subsequent impairments in a self-paced version of the classic 5-choice serial reaction time task, which persisted 14 days after the final drug administration. Longer time points have yet to be examined. These attentional impairments were temporarily reversible by an acute amphetamine (0.5 mg/kg) challenge. Importantly, the attentional deficit was observed after withdrawal from THC, suggesting that the behavioral effects were drug-induced changes in the brain rather than a direct effect of T...