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Effects of GABA(B) receptor agents on cocaine priming, discrete contextual cue and food induced relapses.
Eur J Pharmacol. 2007 Oct 01; 571(2-3):166-73.EJ

Abstract

In the present study we investigated the effects of the GABA(B) receptor antagonist (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), the agonists baclofen and 3-aminopropyl(methyl)phosphinic acid (SKF 97541), and the allosteric positive modulator 3,5-bis(1,1-dimethylethyl)-4-hydroxy-beta,beta-dimethylbenzenepropanol (CGP 7930) on cocaine seeking behavior. The effects of the above drugs on the reinstatement of responding induced by natural reinforcer (food) were also studied. Male Wistar rats were trained to self-administer either cocaine (0.5 mg/kg/infusion) or food (sweet milk) and responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p.), a discrete contextual cue, or a contingent presentation of food. SCH 50911 (3-10 mg/kg) dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned cue reinstatement. At the same time, it failed to alter reinstatement of food-seeking behavior. Baclofen (1.25-5 mg/kg) and SKF 97541 (0.03-0.3 mg/kg) attenuated cocaine- or food-seeking behavior; the effect of the drug appeared more effective for cocaine-seeking than food-seeking. CGP 7930 (10-30 mg/kg) reduced cocaine seeking without affecting food-induced reinstatement on reward seeking. Our results indicate that tonic activation of GABA(B) receptors is required for cocaine seeking behavior in rats. Moreover, the GABA(B) receptor antagonist SCH 50911 was effective in reducing relapse to cocaine at doses that failed to alter reinstatement of food-seeking behavior (present study), basal locomotor activity, cocaine and food self-administration (Filip et al., submitted for publication), suggesting its selective effects on motivated drug-seeking behavior. The potent inhibitory responses on cocaine seeking behavior were also seen following the GABA(B) receptor agonists or the allosteric positive modulator, however, doses of baclofen and SKF 97541 that inhibited cocaine-seeking were only threefold lower of those that inhibited food-seeking. In addition, the direct GABA(B) receptor agonists and the allosteric positive modulator cause decreases in cocaine or food self-administration (Filip et al., submitted for publication), indicating their nonspecific effects on relapse to drug-seeking and drug-taking behavior. In conclusion, the GABA(B) receptor antagonist SCH 50911 seems to be viable treatment for reducing cocaine craving and preventing relapse, while the GABA(B) receptor allosteric positive modulator CGP 7930 may hold the highest promise for attenuating cue-evoked relapses to cocaine as well as the direct rewarding properties of cocaine.

Authors+Show Affiliations

Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, 12 Smetna, Poland. filip@if-pan.krakow.plNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17610868

Citation

Filip, Małgorzata, and Małgorzata Frankowska. "Effects of GABA(B) Receptor Agents On Cocaine Priming, Discrete Contextual Cue and Food Induced Relapses." European Journal of Pharmacology, vol. 571, no. 2-3, 2007, pp. 166-73.
Filip M, Frankowska M. Effects of GABA(B) receptor agents on cocaine priming, discrete contextual cue and food induced relapses. Eur J Pharmacol. 2007;571(2-3):166-73.
Filip, M., & Frankowska, M. (2007). Effects of GABA(B) receptor agents on cocaine priming, discrete contextual cue and food induced relapses. European Journal of Pharmacology, 571(2-3), 166-73.
Filip M, Frankowska M. Effects of GABA(B) Receptor Agents On Cocaine Priming, Discrete Contextual Cue and Food Induced Relapses. Eur J Pharmacol. 2007 Oct 1;571(2-3):166-73. PubMed PMID: 17610868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of GABA(B) receptor agents on cocaine priming, discrete contextual cue and food induced relapses. AU - Filip,Małgorzata, AU - Frankowska,Małgorzata, Y1 - 2007/06/13/ PY - 2007/04/16/received PY - 2007/05/24/revised PY - 2007/05/24/accepted PY - 2007/7/6/pubmed PY - 2007/10/27/medline PY - 2007/7/6/entrez SP - 166 EP - 73 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 571 IS - 2-3 N2 - In the present study we investigated the effects of the GABA(B) receptor antagonist (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), the agonists baclofen and 3-aminopropyl(methyl)phosphinic acid (SKF 97541), and the allosteric positive modulator 3,5-bis(1,1-dimethylethyl)-4-hydroxy-beta,beta-dimethylbenzenepropanol (CGP 7930) on cocaine seeking behavior. The effects of the above drugs on the reinstatement of responding induced by natural reinforcer (food) were also studied. Male Wistar rats were trained to self-administer either cocaine (0.5 mg/kg/infusion) or food (sweet milk) and responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p.), a discrete contextual cue, or a contingent presentation of food. SCH 50911 (3-10 mg/kg) dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned cue reinstatement. At the same time, it failed to alter reinstatement of food-seeking behavior. Baclofen (1.25-5 mg/kg) and SKF 97541 (0.03-0.3 mg/kg) attenuated cocaine- or food-seeking behavior; the effect of the drug appeared more effective for cocaine-seeking than food-seeking. CGP 7930 (10-30 mg/kg) reduced cocaine seeking without affecting food-induced reinstatement on reward seeking. Our results indicate that tonic activation of GABA(B) receptors is required for cocaine seeking behavior in rats. Moreover, the GABA(B) receptor antagonist SCH 50911 was effective in reducing relapse to cocaine at doses that failed to alter reinstatement of food-seeking behavior (present study), basal locomotor activity, cocaine and food self-administration (Filip et al., submitted for publication), suggesting its selective effects on motivated drug-seeking behavior. The potent inhibitory responses on cocaine seeking behavior were also seen following the GABA(B) receptor agonists or the allosteric positive modulator, however, doses of baclofen and SKF 97541 that inhibited cocaine-seeking were only threefold lower of those that inhibited food-seeking. In addition, the direct GABA(B) receptor agonists and the allosteric positive modulator cause decreases in cocaine or food self-administration (Filip et al., submitted for publication), indicating their nonspecific effects on relapse to drug-seeking and drug-taking behavior. In conclusion, the GABA(B) receptor antagonist SCH 50911 seems to be viable treatment for reducing cocaine craving and preventing relapse, while the GABA(B) receptor allosteric positive modulator CGP 7930 may hold the highest promise for attenuating cue-evoked relapses to cocaine as well as the direct rewarding properties of cocaine. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17610868/Effects_of_GABA_B__receptor_agents_on_cocaine_priming_discrete_contextual_cue_and_food_induced_relapses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00682-6 DB - PRIME DP - Unbound Medicine ER -