Several lines of evidence suggest that cannabinoid compounds are anticonvulsant. However, the anticonvulsant potential of cannabinoids and, moreover, the role of the endogenous cannabinoid system in regulating seizure activity has not been tested in an in vivo model of epilepsy that is characterized by spontaneous, recurrent seizures. Here, using the rat pilocarpine model of epilepsy, we show t...

Cannabinoids are known to exert mainly excitatory effects on dopaminergic cells of the ventral tegmental area (VTA). We have utilized an in vivo multiple-single unit electrophysiological approach to assess different neuronal contributions that may ultimately lead to excitation in this area. Baseline neuron recordings, using low impedance microwires, showed a variety of waveforms with a wide ran...

The mesolimbic dopamine system has recently been implicated in the long-term aversive consequences of withdrawal from major drugs of abuse. In the present study we sought to determine whether mesolimbic dopamine neurons are involved in the neurobiologic mechanisms underlying withdrawal from chronic cannabinoid exposure. Rats were treated chronically with the major psychoactive ingredient of has...

Endocannabinoids work as retrograde messengers and contribute to short-term and long-term modulation of synaptic transmission via presynaptic cannabinoid receptors. It is generally accepted that the CB1 cannabinoid receptor (CB1) mediates the effects of endocannabinoid in inhibitory synapses. For excitatory synapses, however, contributions of CB1, "CB3," and some other unidentified receptors ha...

It is known that marijuana smoking and administration of natural cannabinoids reduce intraocular pressure. However, it has not been established whether the intraocular pressure-lowering effects of cannabinoids are mediated by cannabinoid receptors. Aminoalkylindoles are a new class of cannabimimetics with structures entirely different from those of natural cannabinoids. WIN55212-2, a prototypic...

Temporal lobe epilepsy (TLE) is a neurological condition associated with neuron loss, axon sprouting, and hippocampal sclerosis, which results in modified synaptic circuitry. Cannabinoids appear to be anti-convulsive in patients and animal models of TLE, but the mechanisms of this effect are not known. A pilocarpine-induced status epilepticus mouse model of TLE was used to study the effect of c...

The purpose of the experiments was to examine the anxiety-related effects of d-amphetamine and nicotine, and the possible involvement of the endocannabinoid system. D-amphetamine (2 mg/kg, ip) was administered acutely or daily for 8 days. On the 9th day, mice were challenged with d-amphetamine (2 mg/kg, ip) or nicotine (0.1 mg/kg, sc), and were tested in the elevated plus maze. Additionally, a ...

A notable consequence of CB1 cannabinoid receptor activation in vertebrates is an impairment of cognitive function related to learning and short-term memory. The mechanisms of this impairment remain unclear, but one possibility is that cannabinoids influence encoding of stimuli at sensory and/or perceptual levels. Here, by treating zebra finches with the cannabinoid agonist WIN55212-2 and then ...

Anandamide is an putative endogenous cannabinoid ligand that produces pharmacological effects similar to those of Delta9-tetrahydrocannabinol, the principle psychoactive constituent in marijuana. There is considerable evidence that the enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF) is capable of altering the actions of anandamide in vitro by blocking its metabolism. Therefore, studies we...

Excised outside-out patches from HEK293 cells stably transfected with the human (h) 5-HT3A receptor cDNA were used to determine the effects of cannabinoid receptor ligands on the 5-HT-induced current using the patch clamp technique. In addition, binding studies with radioligands for 5-HT3 as well as for cannabinoid CB1 and CB2 receptors were carried out. The 5-HT-induced current was inhibited b...