Several pieces of evidence suggest that the endocannabinoids and dopamine are neurotransmitters sharing physiological roles in the control of locomotion and emotional states. In order to further investigate the functional interactions between these neur...

Cancer patients undergoing chemotherapy treatments often report anticipatory nausea (AN) when they are re-exposed to contextual cues previously paired with treatment. AN is resistant to treatment with classical anti-emetic drugs such as ondansetron (OND...

Epidemiological studies have established that drug use in adolescence is initiated with tobacco and alcohol and progresses to marijuana and other illicit drugs. These findings have led to the hypothesis that alcohol and tobacco are ‘gateway’ drugs that ...

Improgan (a derivative of cimetidine with an unknown mechanism of action) produces antinociception which is reversed by the CB1 receptor antagonist rimonabant and is reduced in THC-tolerant animals, yet improgan has no affinity for the CB1 receptor (Eur...

The CB1R and the Endocannabinoid System (EC) has been shown to play a fundamental role in diet-induced obesity. Δ9 -THC, and the endogenous cannabinoid, (AEA) (N-Arachidonoylethanolamide), have both been shown to stimulate food intake by activating the ...

Dopamine (DA) release onto the nucleus accumbens (NAc) is central to the reward circuit, the dysregulation of which plays a role in addiction. The NAc can be anatomically divided into a core and shell. Both regions receive DA projections from the ventra...

Ventral tegmental area (VTA) dopamine (DA) neurons play a pivotal role in processing reward-related information and are involved in drug addiction and mental illness in humans. Information is conveyed to the VTA in large part by glutamatergic afferents that arise in various brain nuclei, including the pedunculopontine nucleus (PPN). Using a unique rat brain slice preparation, we found that PPN stimulation activates afferents targeting GluR2-containing AMPA receptors (AMPAR) on VTA DA neurons, and these afferents did not exhibit long-term depression (LTD). In contrast, activation of glutamate afferents onto the same DA neurons via stimulation within the VTA evoked EPSCs mediated by GluR2-lacking AMPARs that demonstrated LTD or EPSCs mediated by GluR2-containing AMPA receptors that did not express LTD. Twenty-four hours after single cocaine injections to rats, GluR2-lacking AMPARs were increased at both PPN and local VTA projections, and this permitted LTD expression in both pathways. Single injections with ...

Ack1 correspond to a new subfamily of tyrosine kinases having several protein-protein interaction domains: an SH3 domain, a region able to interact with Cdc42 (Cbd domains: Cdc42 binding domain) and several proline riche regions. In previous work we hav...

There is evidence that i.c.v. infusion of the â-amyloid (Aâ) 1-42 peptide fragment (BAP 1-42) may cause brain dysfunction as evidenced by neurodegeneration and impairment of learning and memory, typical symptoms of Alzheimer’s disease. Neurodegeneration affects subcortical nuclei involved in cognitive behavior and disrupt cholinergic neurotransmission in these nuclei. Endogenous cannabinoids decrease brain ACh levels and may induce a deficit of memory capacity. These effects are mediated by the activation of CB1 cannabinoid receptors. In fact, administration of the selective CB1 cannabinoid receptor antagonist, SR141716A, reversed in mice the cognitive impairment induced by cannabinoids, such as marijuana and its active ingredient Ä9 – tetrahydrocannabinol, or endogenous cannabinoids, such as anandamide. SR141716A also counteracted the amnesia induced by BAP 1-42 in the passive avoidance paradigm. It is likely that a direct correlation exists between the amnesic effect induced by Aâ and cerebral CB1 action...

Feeding behavior is one of most important motivated behaviors and the most potent drive for feeding is its reward nature in human and mammal. The lateral hypothalamus is critical for regulation of feeding behavior and is considered an important structure for the brain reward circuitry. Synaptic interactions within the hypothalamus per se as well as the activity of the feeding-related projection neurons in the lateral hypothalamus are subject to extensive modulation. Despite the well-known physiological effects of nicotine and delta9(-)-tetrahydrocannabinol (THC) administered exogenously, relatively little is known of the hypothalamic actions of their endogenous counterparts. Our present study provided a neurophysiological analysis of the modulation of the excitability of melanin-concentrating hormone (MCH) synthesizing neurons in the lateral hypothalamus (LH) implicated in natural reward behavior. We first identified MCH neurons based on the electrophysiological profile. MCH neurons showed a strong accommo...