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Rewarding Properties (rewarding + property)
Selected AbstractsGENETIC STUDY: An association of prodynorphin polymorphisms and opioid dependence in females in a Chinese populationADDICTION BIOLOGY, Issue 3 2009Toni-Kim Clarke ABSTRACT Prodynorphin (PDYN) binds to ,-opioid receptors and is known to regulate dopaminergic tone, making this system important for the reinforcing and rewarding properties of drugs of abuse such as opioids. The binding of dynorphins to ,-opioid receptors also produces aversive states that may affect the development of opioid dependence. Recent animal results have shown that PDYNknockout mice show decreased ethanol consumption; however, this finding was restricted to female mice. We were interested to analyse a possible gender specificity of dynorphin effects in humans and to this end three single-nucleotide polymorphisms (SNPs) in PDYN were genotyped in a Chinese population of 484 opioid dependents and 374 controls. An interaction between sex and genotype was found in female opioid dependents. Chi-squared tests for association revealed that the genotype distributions of SNPs rs1997794 (P = 0.019) and rs1022563 (P = 0.006) in the promoter and 3, region of PDYN, respectively, were found to be associated with opioid dependence. Therefore, SNPs in PDYN are significantly associated with the risk of developing opioid dependence; however, this effect may only be seen in females. These data suggest that PDYN polymorphisms should be studied in additional female opioid-dependent populations with an emphasis on the promoter and 3, regions of the gene. [source] The Endocannabinoid System and Energy MetabolismJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008L. Bellocchio Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors [cannabinoid receptor type 1 (CB1) and CB2] participate in the physiological modulation of many central and peripheral functions. The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received considerable attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptors and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, and therefore drugs interfering with this overactivation by blocking CB1 receptors are considered as potentially valuable candidates for the treatment of obesity and related cardiometabolic risk factors. [source] Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathwayJOURNAL OF PINEAL RESEARCH, Issue 4 2007Noushin Yahyavi-Firouz-Abadi Abstract:, Melatonin has different interactions with opioids including the enhancement of the analgesic effects of morphine and also reversal of tolerance and dependence to morphine. The present study assessed the effect of melatonin on morphine reward in mice using a conditioned place preference (CPP) paradigm. Our data showed that subcutaneous administration of morphine (1,7.5 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal (i.p.) administration of melatonin (1,40 mg/kg) alone did not induce either CPP or conditioned place aversion (CPA), while the combination of melatonin (5,20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to rewarding effect. We further investigated the involvement of the nitric oxidergic pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric oxide synthase inhibitor, NG -nitro- l -arginine methyl ester (l -NAME). l -NAME (1 and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show any significant CPP or CPA. Co-administration of l -NAME (5 mg/kg) with an ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced significant CPP that may imply the similarity of action of melatonin and l -NAME and involvement of the nitric oxidergic pathway in this regard. Our results indicate that pretreatment of animals with melatonin enhances the rewarding properties of morphine via a mechanism which may involve the nitric oxidergic pathway. [source] Ethanol-Induced Conditioned Taste Avoidance: Reward or Aversion?ALCOHOLISM, Issue 3 2009Chuang Liu Background:, Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. Methods:, In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague,Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Results:, Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. Conclusion:, The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose. [source] Reduction of Ethanol-Derived Acetaldehyde Induced Motivational Properties by l -CysteineALCOHOLISM, Issue 1 2009Alessandra T. Peana Background:, Experimental evidences suggest that acetaldehyde (ACD) contributes to the positive motivational properties of ethanol (EtOH) as assessed by the place conditioning paradigm; indeed, we found that by reducing ACD production and/or by using ACD-sequestrating agents, EtOH is deprived from its motivational properties. Thiol products, such as the amino acid cysteine, are known to be effective ACD-sequestering agents. Cysteine is able to covalently bind ACD thereby forming a stable, nontoxic 2-methyl-thiazolidine-4-carboxylic acid compound. Thus, we treated rats with l -cysteine before intragastric administration of EtOH or ACD. Methods:, Male Wistar rats were pretreated intraperitoneally with saline or l -cysteine (10, 20, or 30 mg/kg), before intragastric administration of saline, EtOH (1 g/kg), or ACD (20 mg/kg). The specificity of l -cysteine effect was addressed using morphine-induced conditioned place preference (cpp) (2.5 mg/kg, i.p.). Results:,l -cysteine dose-dependently prevented both EtOH and ACD-induced cpp but did not interfere with morphine-induced cpp, suggesting that l -cysteine specifically modulates the motivational properties of EtOH. Conclusion:, The present results further underscore the role of EtOH-derived ACD in EtOH-induced motivational properties. l -cysteine, by binding EtOH-derived ACD, would deprive it of its rewarding properties and reduce its abuse liability. [source] Cholinergic axons in the rat ventral tegmental area synapse preferentially onto mesoaccumbens dopamine neuronsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2006Natalia Omelchenko Abstract Cholinergic afferents to the ventral tegmental area (VTA) contribute substantially to the regulation of motivated behaviors and the rewarding properties of nicotine. These actions are believed to involve connections with dopamine (DA) neurons projecting to the nucleus accumbens (NAc). However, this direct synaptic link has never been investigated, nor is it known whether cholinergic inputs innervate other populations of DA and ,-aminobutyric acid (GABA) neurons, including those projecting to the prefrontal cortex (PFC). We addressed these questions by using electron microscopic analysis of retrograde tract-tracing and immunocytochemistry for the vesicular acetylcholine transporter (VAChT) and for tyrosine hydroxylase (TH) and GABA. In tissue labeled for TH, VAChT+ terminals frequently synapsed onto DA mesoaccumbens neurons but only seldom contacted DA mesoprefrontal cells. In tissue labeled for GABA, one-third of VAChT+ terminals innervated GABA-labeled dendrites, including both mesoaccumbens and mesoprefrontal populations. VAChT+ synapses onto DA and mesoaccumbens neurons were more commonly of the asymmetric (presumed excitatory) morphological type, whereas VAChT+ synapses onto GABA cells were more frequently symmetric (presumed inhibitory or modulatory). These findings suggest that cholinergic inputs to the VTA mediate complex synaptic actions, with a major portion of this effect likely to involve an excitatory influence on DA mesoaccumbens neurons. As such, the results suggest that natural and drug rewards operating through cholinergic afferents to the VTA have a direct synaptic link to the mesoaccumbens DA neurons that modulate approach behaviors. J. Comp. Neurol. 494:863,875, 2006. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||