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Drug Reward (drug + reward)
Selected AbstractsCognitive enhancement as a pharmacotherapy target for stimulant addictionADDICTION, Issue 1 2010Mehmet Sofuoglu ABSTRACT Background No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. Aim To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Methods Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Results and conclusions Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha2 -adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction. [source] Effects of MPEP on expression of food-, MDMA- or amphetamine-conditioned place preference in ratsADDICTION BIOLOGY, Issue 3 2005Volker Herzig Recent studies have revealed the effectiveness of 2-methyl-6-(phenylethynyl)pyridine (MPEP), a highly selective antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), in conditioned drug reward. In a previous study we showed that MPEP blocks expression of context-conditioned morphine- but not cocaine reward in the rat. The present study now examines the effectiveness of MPEP in the expression of context-conditioned food, MDMA (,ecstasy?) or amphetamine reward. Therefore, three groups of rats were conditioned either to food, MDMA or amphetamine in the conditioned place preference (CPP) paradigm. After conditioning, CPP expression and locomotion were determined simultaneously in the presence and absence of the respective reward (i.e. food or drug), or after application of 50?mg/kg MPEP (the dose that was most effective in reducing morphine CPP expression in our previous study). As a result, MPEP reduced locomotion in all groups. Furthermore, only expression of amphetamine CPP was inhibited by MPEP, while expression of food and MDMA CPP was not affected, suggesting that the MPEP-induced inhibition of amphetamine CPP expression was not causally linked to the reduction of locomotion. Overall, we conclude that MPEP reduces expression of context-conditioned amphetamine but not MDMA or food reward. [source] Ethanol enhancement of cocaine- and amphetamine-regulated transcript mRNA and peptide expression in the nucleus accumbensJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Armando Salinas Abstract Cocaine- and amphetamine-regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contribute to rewarding behaviors and the addiction liability of psychostimulants; however, there are no reports of basic work concerning CART in relation to alcohol and mechanisms of alcohol dependence development. Therefore, in this study we investigated the response of CART transcript and peptide to acute ethanol administration in vivo. Rats were administered ethanol (1 g/kg or 3.5 g/kg, 1 h, ip) and CART expression was measured by RT-PCR in the nucleus accumbens (NAcc). Ethanol (3.5 g/kg) increased CART transcription markedly. The interactions of dopamine on ethanol-induced CART expression were further evaluated pharmacologically using D1 and D2/D3 receptor antagonists. Both SCH 23390 (0.25 mg/kg) or raclopride (0.2 mg/kg) pre-treatment significantly suppressed ethanol-enhancement of CART mRNA transcription. Confocal immunofluorescence microscopy revealed that CART peptide immunoreactivity was also enhanced in both the core and the shell of the NAcc by ethanol administration. These findings demonstrate that CART mRNA and peptide expression are responsive to acute ethanol administrated in vivo and suggests that CART peptides may be important in regulating the rewarding and reinforcing properties of ethanol. [source] Acute and Chronic Ethanol Modulate Dopamine D2-Subtype Receptor Responses in Ventral Tegmental Area GABA NeuronsALCOHOLISM, Issue 5 2009Kimberly H. Ludlow Background:, Ventral tegmental area (VTA) ,-aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption. Methods:, Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT-polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair-fed controls. Results:, In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down-regulation in the expression of D2 receptors in ethanol-consuming rats versus pair-fed controls. Conclusions:, Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down-regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons. [source] | |||||||||||||