In vitro pharmacological characterization of RXFP3 allosterism: an example of probe dependency.

Recent findings suggest that the relaxin-3 neural network may represent a new ascending arousal pathway able to modulate a range of neural circuits including those affecting circadian rhythm and sleep/wake states, spatial and emotional memory, motivation and reward, the response to stress, and feeding and metabolism. Therefore, the relaxin-3 receptor (RXFP3) is a potential therapeutic target for the treatment of various CNS diseases. Here we describe a novel selective RXFP3 receptor positive allosteric modulator (PAM), 3-[3,5-Bis(trifluoromethyl)phenyl]-1-(3,4-dichlorobenzyl)-1-[2-(5-methoxy-1H-indol-3-yl)ethyl]urea (135PAM1).

Chronic ethanol treatment potentiates ethanol-induced increases in interstitial nucleus accumbens endocannabinoid levels in rats.

We employed in vivo microdialysis to characterize the effect of an ethanol challenge injection on endocannabinoid levels in the nucleus accumbens of ethanol-naïve and chronic ethanol-treated rats. Ethanol (0.75 and 2 g/kg, i.

Regional Influence of Cannabinoid CB Receptors in the Regulation of Ethanol Self-Administration by Wistar Rats.

Substantial evidence suggests a facilitatory influence of cannabinoid CB receptors in the modulation of ethanol consumption by rodents. Studies performed in rats selectively bred for high alcohol preference point to an involvement of CB receptors in the nucleus accumbens (NAC), ventral tegmental area (VTA) and medial prefrontal cortex (mPFC) in the modulation ethanol self-administration. However, the neural mechanisms through which CB receptors regulate ethanol intake in out-bred Wistar rats have not been investigated.

Attenuation of cue-induced heroin-seeking behavior by cannabinoid CB1 antagonist infusions into the nucleus accumbens core and prefrontal cortex, but not basolateral amygdala.

As with other drugs of abuse, heroin use is characterized by a high incidence of relapse following detoxification that can be triggered by exposure to conditioned stimuli previously associated with drug availability. Recent findings suggest that cannabinoid CB(1) receptors modulate the motivational properties of heroin-conditioned stimuli that induce relapse behavior. However, the neural substrates through which CB(1) receptors modulate cue-induced heroin seeking have not been elucidated.

Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration.

Ethanol and opiate self-administration are sensitive to manipulations of cannabinoid CB1 receptor function and, from this, a role for the endogenous cannabinoid system in the modulation of drug reward has been hypothesized. However, direct in vivo evidence of drug-induced alterations in brain endocannabinoid (eCB) formation has been lacking. To address this issue, we explored the effect of drug self-administration on interstitial eCB levels in the nucleus accumbens (NAc) shell using in vivo microdialysis.

Regulation of brain anandamide by acute administration of ethanol.

The endogenous cannabinoid acylethanolamide AEA (arachidonoylethanolamide; also known as anandamide) participates in the neuroadaptations associated with chronic ethanol exposure. However, no studies have described the acute actions of ethanol on AEA production and degradation. In the present study, we investigated the time course of the effects of the intraperitoneal administration of ethanol (4 g/kg of body mass) on the endogenous levels of AEA in central and peripheral tissues.

Contributions of the mitogen-activated protein kinase and protein kinase C cascades in spatial learning and memory mediated by the nucleus accumbens.

Several studies have reported a role for the nucleus accumbens (NAcc) in learning and memory. Specifically, NAcc seems to function as a neural bridge for the translation of corticolimbic information to the motor system mediating locomotor learning, but the signaling mechanisms involved in this striatal learning await further investigation. The present experiments investigated the role of the mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) cascades within the NAcc of Long-Evans rats in a food-search spatial learning task (FSSLT).

Spatial learning in rats is impaired by microinfusions of protein kinase C-gamma antisense oligodeoxynucleotide within the nucleus accumbens.

The nucleus accumbens (NAcc) has been shown to play a role in motor and spatial learning. Protein kinase C (PKC) has been implicated in the mechanisms of initiation and maintenance of long-term potentiation that is thought to be involved in the storage of long-term memory. In the present study, the importance of de novo synthesis of PKC-gamma within the NAcc in the acquisition and retention of spatial discrimination learning was assessed using an antisense knockdown approach.