Symmetrical generalization between the discriminative stimulus effects of gamma-hydroxybutyric acid and ethanol: occurrence within narrow dose ranges. Physiol Behav 57: 105-111

Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell, 4, 09124 Cagliari, Italy
Physiology & Behavior (Impact Factor: 2.98). 02/1995; 57(1):105-111. DOI: 10.1016/0031-9384(94)00215-Q


Gamma-hydroxybutyric acid (GHB) has been shown to reduce ethanol consumption and suppress ethanol withdrawal syndrome both in laboratory animals and humans. The present study was designed to assess the similarity between the discriminative stimulus effects, or subjective feelings, of GHB and ethanol using a T-maze, food-reinforced drug discrimination procedure. Three groups of rats were trained to discriminate ethanol (1.0 or 2.0 g/kg; p.o.) or GHB (300 mg/kg; p.o.) from water. In the 1.0 g/kg ethanol-trained rats, substitution for ethanol was an inverted U-shape function of GHB dose, with only 300 mg/kg GHB resulting in complete substitution for ethanol. No dose of GHB elicited selection of ethanol-appropriate arm higher than 10% in the 2.0 g/kg ethanol-trained group. In the 300 mg/kg GHB-trained rats, complete substitution for GHB occurred only at the dose of 1.0 g/kg ethanol. Doses of ethanol lower or higher than 1.0 g/kg did not substitute for GHB. The results of the present study indicate that symmetrical generalization between ethanol and GHB occurred within narrow dose ranges. They are discussed in terms of common neurotransmitter systems involved in the mediation of GHB and ethanol effects.

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    • "In a line of elegant behavioral pharmacology work, France and colleagues demonstrated that GHB exerts its effect primarily through the GABAb receptor, although other sites also contribute to GHB's effect (e.g., Carter, Koek & France, 2009; Koek, Mercer, Coop & France, 2009). Drug discrimination studies with ethanol and GHB have yielded mixed results, with cross generalization occurring between the two substances but only within a narrow range of doses (Colombo et al., 1995). "
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    ABSTRACT: Gamma-hydroxybutyrate (GHB) is a drug with significant abuse potential. The present study aimed to assess the relative value of escalating doses of GHB to current GHB users via the Multiple Choice Procedure (MCP), and to validate that the dose rated highest with the MCP would be self-administered at a greater rate than placebo. Participants were 5 current GHB users who were not currently trying to stop using GHB. To examine the value of escalating doses of GHB, the following doses of GHB were used: 0 (placebo), 12.5, 25, 37.5, and 50 mg/kg. Participants typically assigned higher doses of GHB had higher crossover points on the MCP. During choice sessions, participants made repeated choices between administering GHB, placebo or nothing. All participants selected GHB exclusively (5 out of 5 instances) except for one participant who selected GHB on 4 out of 5 instances, thus 96% (i.e., 24/25) of choices were for active GHB. Based on these data, GHB appears likely to function as a dose-dependent reinforcer for humans based on our sample.
    Journal of the Experimental Analysis of Behavior 05/2012; 97(3):323-31. DOI:10.1901/jeab.2012.97-323 · 1.87 Impact Factor
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    • "However, GHB did not occasion drug-appropriate responding in all drug discrimination procedures in which it was studied. GHB did not occasion more than 30% drug-appropriate responding in animals discriminating d-amphetamine, phencyclidine, heroin, positive GABA A receptor modulators (e.g., triazolam, diazepam, pentobarbital), and, in some cases, ethanol (Table 1;Colombo et al., 1995d;Shelton, 2004). Likewise, GBL and 1,4-BD did not occasion drug-appropriate responding in animals trained to discriminate pentobarbital, midazolam, or diazepam (McMahon et al., 2003;Carter et al., 2004a). "
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    ABSTRACT: GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABAB receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABAB receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABAA and GABAB receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects.
    Pharmacology [?] Therapeutics 11/2008; 121(1):100-14. DOI:10.1016/j.pharmthera.2008.10.003 · 9.72 Impact Factor
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    • "Previous studies have also reported a lack of or inconsistent decreases in response rate with GHB except with very high doses. For example, 1500 mg/kg (i.g.) GHB decreased response rates in rats (Colombo et al. 1995). On the other hand, Baker et al. (2004) reported minor decreases in rats' response rates after 75–400 mg/kg GHB (i.g.), with the greatest mean percent decrease approximating 50%. "
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    ABSTRACT: Gamma-hydroxybutyric acid has been proposed as a pharmacotherapy for alcoholism in part based on similar discriminative stimulus effects as ethanol. To date, drug discrimination studies with gamma-hydroxybutyric acid and ethanol have exclusively used rodents or pigeons as subjects. To evaluate possible differences between species, sex, and route of administration, this study investigated the substitution of gamma-hydroxybutyric acid (intragastrically or intramuscularly) for ethanol 30 or 60 min after administration in male (n=6) and female (n=7) cynomolgus monkeys trained to discriminate 1.0 and 2.0 g/kg ethanol. At least one dose of gamma-hydroxybutyric acid completely or partially substituted for ethanol in three of the 13 monkeys tested, with each case occurring in female monkeys. Ethanol-appropriate responding did not increase with gamma-hydroxybutyric acid dose. Monkeys were more sensitive to the response rate decreasing effects of gamma-hydroxybutyric acid administered intramuscularly compared with intragastrically. The lack of gamma-hydroxybutyric acid substitution for ethanol suggests that these drugs have different receptor bases for discrimination. Furthermore, the data do not strongly support shared discriminative stimulus effects as the rationale for gamma-hydroxybutyric acid pharmacotherapy for alcoholism.
    Behavioural Pharmacology 08/2008; 19(4):317-24. DOI:10.1097/FBP.0b013e328308f20d · 2.15 Impact Factor
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