This study characterized the antinociceptive, respiratory and heart rate effects of the cannabinoid receptor agonists Delta-9-tetrahydrocannabinol (Delta-9-THC) and WIN 55212 ((R)-(+)-2, 3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol-[1,2,3-de]-1, 4-benzoxazin-6-yl)(1-naphtalenyl)methanone monomethanesulfonate), N-arachidonyl ethanolamide (anandamide) and the mu and kappa opioid receptor ago...

Although the cannabinoid agonists R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)-(1-naphthalenyl) methanone mesylate [WIN 55,212-2 (WIN)] and (R,S)-3-(2-iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinylmethyl)-1H-indole (AM1241) exert peripheral antihyperalgesia in inflammatory pain models, the mechanism for cannabinoid-induced inhibition of nociceptive s...

Amino acid residues in the transmembrane domains of the CB(1) receptor are important for ligand recognition and signal transduction. We used site-directed mutagenesis to identify the role of two novel and adjacent residues in the transmembrane helix II domain, Ile2.62 and Asp2.63. We investigated the role of the conserved, negatively charged aspartate at position 2.63 in cannabinoid receptor (C...

Benzoxazinoids have been described as important allelochemicals from Gramineae as well as Acanthaceae, Rannunculaceae, and Scrophulariaceae plants. Several bioactivities have been described and evaluated for these compounds, including fungistatic, antifeedant, and phytotoxic. In ongoing studies about allelochemicals as natural herbicide models, the description of soil dynamics in phytotoxic age...

Endocannabinoid signaling in the dorsal raphe (DR) has recently been implicated in the regulation of anxiety and depression. However, the cellular mechanisms by which endocannabinoids (eCBs) regulate the excitability of DR 5-hydroxytryptamine (serotonin; 5-HT) neurons remain poorly understood. In the present study, using whole-cell recording from DR 5-HT neurons, we examined the effects of eCBs...

BACKGROUND The adolescent brain is sensitive to experience-dependent plasticity and might be more vulnerable than the adult brain to the effects of some drugs of abuse. The factors that contribute to these differences are not fully identified. We have examined the ability of cannabinoids to induce a form of synaptic plasticity, long-term depression, in the nucleus accumbens and dorsolateral str...

Receptor internalization increases the flexibility and scope of G protein-coupled receptor (GPCR) signaling. CB(1) and CB(2) cannabinoid receptors undergo internalization after sustained exposure to agonists. However, it is not known whether different agonists internalize CB(2) to different extents. Because CB(2) is a promising therapeutic target, understanding its trafficking in response to di...

The effects of cannabinoid receptor agonists and antagonists on smooth muscle resting membrane potentials and on membrane potentials following electrical neuronal stimulation in a myenteric neuron/smooth muscle preparation of wild-type and cannabinoid receptor type 1 (CB1)-deficient mice were investigated in vitro. Double staining for CB1 and nitric oxide synthase (neuronal) was performed to id...

Delta9-tetrahydrocannabinol (Delta9-THC) is the principal psychoactive ingredient in marijuana. We examined the effects of Delta9-THC on glutamatergic synaptic transmission. Reducing the extracellular Mg++ concentration bathing rat hippocampal neurons in culture to 0.1 mM elicited a repetitive pattern of glutamatergic synaptic activity that produced intracellular Ca++ concentration spikes that ...