GABAB Receptors in Reward Processes

Vlachou, Styliani; Markou, Athina

doi:10.1016/s1054-3589(10)58013-x

Cited by 103 publications

(83 citation statements)

References 152 publications

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“…Rats receiving these microinjections were more sensitive to the rewarding effects of ethanol. Considering that the enhanced preference to drug-paired environments and rewarding effects of psycho-stimulants appear to depend on common neural substrates (Green and Grahame, 2008;McBride et al, 1999;Risinger et al, 1994;Vlachou and Markou, 2010), these findings raised the possibility that reduced expression of mGlu7 receptors in the mesolimbic system would also affect the rewarding effects of ethanol. Indeed, lower doses of alcohol established-conditioned-place preferences in rats given this treatment, suggesting that these rats were more sensitive to the rewarding effects of the drug.…”

Section: Discussionmentioning

confidence: 99%

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Bahí

2012

Neuropsychopharmacol

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Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotorstimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol.

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Section: Discussionmentioning

confidence: 99%

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Bahí

2012

Neuropsychopharmacol

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“…Such receptor heterogeneity would allow more selective manipulation of the GABA B system. GABA B receptor-positive modulators are thought to have advantages as potential medications for anxiety, depression, and drug addiction (Cryan et al, 2004;Frankowska et al, 2007;Jacobson and Cryan, 2008;Vlachou and Markou, 2010), because they may have a better side effect profile than GABA B receptor agonists, based on the notion that selective enhancement of activated receptors has effects that differ from indiscriminate activation of all receptors. Unlike baclofen, GABA B receptor-positive modulators do not seem to interfere with motor coordination (Cryan et al, 2004;Jacobson and Cryan, 2008), do not produce loss of righting (Carai et al, 2004;Malherbe et al, 2008;Koek et al, 2010) and, with the possible exception of CGP7930 (Koek et al, 2010), do not induce hypothermia (Jacobson and Cryan, 2008;Malherbe et al, 2008;Koek et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Effects of the GABA_B Receptor-Positive Modulators CGP7930 and rac-BHFF in Baclofen- and γ-Hydroxybutyrate-Discriminating Pigeons

Koek¹,

Cheng

Rice

2012

J Pharmacol Exp Ther

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In vivo effects of GABA B receptor-positive modulators suggest them to have therapeutic potential to treat central nervous system disorders such as anxiety and drug abuse. Although these effects are thought to be mediated by positive modulation of GABA B receptors, such modulation has been examined primarily in vitro. This study further examined the in vivo properties of the GABA B receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl) phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF). In pigeons discriminating baclofen from saline, ␥-hydroxybutyrate (GHB) produced 100% baclofen-appropriate responding, and the GABA B antagonist 3-aminopropyl(dimethoxymethyl) phosphinic acid (CGP35348) blocked the effects of both drugs. CGP7930 and rac-BHFF produced at most 41 and 74% baclofen-appropriate responding, respectively, and enhanced the discriminative stimulus effects of baclofen, but not of GHB. In pigeons discriminating GHB from saline, CGP7930 and rac-BHFF produced at most 1 and 49% GHB-appropriate responding, respectively, and enhanced the effects of baclofen, but not of GHB. Enhancement of the discriminative stimulus effects of baclofen by rac-BHFF and CGP7930 is further evidence of their effectiveness as GABA B receptor-positive modulators in vivo. Furthermore, lack of complete substitution of the positive modulators rac-BHFF and CGP7930 for baclofen and GHB suggests that their discriminative stimulus effects differ from those of GABA B receptor agonists. Finally, together with converging evidence that the GABA B receptor populations mediating the effects of baclofen and GHB are not identical, the present findings suggest that these populations differ in their susceptibility to positive modulatory effects. Such differences could allow for more selective therapeutic targeting of the GABA B system.

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“…g-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system, and it binds to two major receptor types, the GABA A and GABA B receptors (Charney et al, 2006;Vlachou and Markou, 2010). GABA A receptors are ligand-gated chloride channels, and because extracellular chloride concentrations are usually greater than intracellular concentrations in neurons, activation of GABA A receptors usually causes an influx of negatively charged chloride anions that hyperpolarizes neurons and reduces neuronal excitability (Farrant and Nusser, 2005;Egawa and Fukuda, 2013).…”

Section: Gabaergic Drugsmentioning

confidence: 99%

“…A variety of other chemicals including ethanol and some volatile inhalants (e.g., toluene) also positively modulate GABA A receptor function. GABA B receptors are G i/o -protein-coupled receptors that exist as dimers of two GABA B subunits linked to inhibitory signaling pathways, including calcium channel inhibition, potassium channel activation, and inhibition of adenylate cyclase (Vlachou and Markou, 2010;Benarroch, 2012). The only clinically available GABA B ligand is the agonist baclofen, but other drugs have been developed that function as agonists, antagonists and allosteric modulators.…”

Section: Gabaergic Drugsmentioning

confidence: 99%

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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GABAB Receptors in Reward Processes

Cited by 103 publications

References 152 publications

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Effects of the GABA_B Receptor-Positive Modulators CGP7930 and rac-BHFF in Baclofen- and γ-Hydroxybutyrate-Discriminating Pigeons

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

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GABAB Receptors in Reward Processes

Cited by 103 publications

References 152 publications

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Effects of the GABAB Receptor-Positive Modulators CGP7930 and rac-BHFF in Baclofen- and γ-Hydroxybutyrate-Discriminating Pigeons

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

Contact Info

Product

Resources

About

Effects of the GABA_B Receptor-Positive Modulators CGP7930 and rac-BHFF in Baclofen- and γ-Hydroxybutyrate-Discriminating Pigeons