High school science laboratories have historically faced obstacles including limited funds, “boring” topics, and cookbook-style approaches. To address these issues, we have developed Rex, a web-based platform that allows students to conduct virtual expe...

AM1710, a cannabilactone CB2 agonist, has shown promising anti-allodynic efficacy in suppressing neuropathic pain without producing tolerance or unwanted side effects associated with CB1 receptors (Deng, et al. (2015) Biological Psych 77: 475-87). In th...

Recent studies have suggested L-DOPA-induced dyskinesia (LID) may be related to an inflammatory environment, which involves glial cells activation in the striatum. This pro-inflammatory environment may result from excessive levels of glutamate and dopam...

The mechanisms of behavioral responses to abusive substances are not fully understood. For example, cannabinoids and related drugs generate profound analgesic effects through activating the cannabinoid receptor type 1 (CB1R). However, repeated cannabino...

Voltage-gated Cav2.1 (P/Q-type) Ca2+ channels undergo Ca2+- dependent inactivation (CDI) and facilitation (CDF), respectively, which contribute to short-term synaptic plasticity. Both CDI and CDF are mediated by calmodulin (CaM) binding to sites in the ...

Dopaminergic neurotransmission has been highly implicated in the reinforcing properties of many substances of abuse, including marijuana. Cannabinoids activate ventral tegmental area dopaminergic neurons, the main ascending projections of the mesocorticolimbic dopamine system, and change their spiking pattern by increasing the number of impulses in a burst and elevating the frequency of bursts. Although they also increase time-averaged striatal dopamine levels for extended periods of time, little is known about the temporal structure of this change. To elucidate this, fast-scan cyclic voltammetry was used to monitor extracellular dopamine in the nucleus accumbens of freely moving rats with subsecond timescale resolution. Intravenous administration of the central cannabinoid (CB1) receptor agonist, R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl) methanone mesylate, dose-dependently produced catalepsy, decreased locomotion, and reduced the amplitude ...

Endocannabinoid signaling is distributed throughout the brain, regulating synaptic release of both excitatory and inhibitory neurotransmitters. The presence of endocannabinoid signaling within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures such as the amygdala, suggests it may play an important role in regulating the neuroendocrine and behavioral effects of stress. The evidence reviewed here demonstrates that endocannabinoid signaling is involved in both activating and terminating the hypothalamic-pituitary-adrenal axis response to both acute and repeated stress. In addition to neuroendocrine function, however, endocannabinoid signaling is also recruited by stress and glucocorticoid hormones to modulate cognitive and emotional processes such as memory consolidation and extinction. Collectively, these data demonstrate the importance of endocannabinoid signaling at multiple levels as both a regulator and an effector of the stress response.

Schizophrenia is a debilitating disease that affects up to 1% of the population with an onset of symptoms starting in late adolescence to early adulthood. This is also a period of development when many adolescents experiment with drugs and abuse cannabi...

Over 150 mutations in the SCN2A gene, which encodes the neuronal Nav1.2 protein, have been implicated in human epilepsy cases. Of these, R1882Q and R853Q are two of the most commonly reported mutations. This study utilized voltage-clamp electrophysiology to characterize the biophysical effects of the R1882Q and R853Q mutations on the hNav1.2 channel, including their effects on resurgent current and gating pore current, which are not typically investigated in the study of Nav1.2 channel mutations. HEK cells transiently transfected with DNA encoding either wild-type (WT) or mutant hNav1.2 revealed that the R1882Q mutation induced a gain-of-function phenotype, including slowed fast inactivation, depolarization of the voltage dependence of inactivation, and increased persistent current. In this model system, the R853Q mutation primarily produced loss-of-function effects, including reduced transient current amplitude and density, hyperpolarization of the voltage dependence of inactivation, and decreased persist...

Nausea and vomiting are distressing side effects of chemotherapy treatment for cancer. Currently available first-line anti-emetic therapies (in particular 5-HT3 antagonists) have been critical in reducing these side effects, however, nausea in particula...