Drug discrimination analysis of ethanol as an N-methyl-D-aspartate receptor antagonist

Balster, Robert L.; Grech, Doreen M.; Bobelis, D J

doi:10.1016/0014-2999(92)90460-l

Cited by 30 publications

(9 citation statements)

References 16 publications

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“…It is known that the substitution of the ethanol cue by noncompetitive NMDA-antagonists acting at the ion channel is not symmetrical. For example, ethanol does not show complete generalization to either the dizocilpine cue in pigeons (Butelman et al 1993) or the PCP cue in rats (Balster et al 1992;Grant and Colombo 1993a) trained to discriminate dizocilpine or PCP, respectively, from saline. These results, together with the failure of ethanol to fully substitute for the cues of NPC 12626 (Balster et al 1992) or CGS 19755 (cis-4-(phosphonomethyl)piperidine-2-carboxylic acid) (Butelman et al 1993), which are both potent competitive NMDA antagonists, raises the question whether ethanol acts not only via the NMDA agonist and the NMDA channel-binding sites, but also via other binding sites at the NMDA receptor or via other glutamate receptors such as the AMPA receptor.…”

Section: Discussionmentioning

confidence: 97%

Ethanol and N -methyl- D -aspartate receptor complex interactions: a detailed drug discrimination study in the rat

et al. 1998

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The discriminative stimulus properties of compounds that interact with the NMDA receptor complex were investigated in rats trained to discriminate ethanol from saline. Male Wistar rats were trained in a two-lever operant drug discrimination paradigm to make differential responses [fixed ratio 10 (FR10)] for food after ethanol (1 g/kg i.p.; 12% v/v ethanol solution) and saline vehicle injections. Drug effects were assessed by means of generalization and antagonism tests. In the generalization tests, the noncompetitive NMDA antagonists acting at the ion channel dizocilpine, memantine, phencyclidine (PCP) and the sigma1 receptor agonists (+)-pentazocine and (+)-N-allyl-normetazocine (NANM) dose-dependently generalized for ethanol, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) antagonist GYKI 52466, the glycine antagonists L-701,324 and MRZ 2/502, the polyamine site antagonist arcaine and the polyamine site ligand spermidine, did not. Our results show that the noncompetitive NMDA antagonists fully substitute dose-dependently for ethanol in a drug-discrimination task. The ethanol-like discriminative stimulus effects of PCP, pentazocine and NANM, which are also sigma receptor ligands, are likely to be attributed to their activity at NMDA receptors. We therefore assume that some of the acute effects of ethanol are mediated via NMDA receptor antagonism at the PCP binding site.

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Section: Discussionmentioning

confidence: 97%

Ethanol and N -methyl- D -aspartate receptor complex interactions: a detailed drug discrimination study in the rat

et al. 1998

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“…First is the finding that a variety of different NMDA receptor antagonists, with different interoceptive and behavioral effects, all have the ability to inhibit the development of tolerance. For example, in drug discrimination studies, which is a common test for interoceptive effects of drugs, there is little generalization among compounds acting at the different sites on the NMDA receptor complex (Jackson and Sanger 1988;Willetts et al , 1991Koek et al 1990;Singh et al 1990;Mansbach and Balster 1991;Balster et al 1992Balster et al , 1994Bobelis and Balster 1993;Gold and Balster 1993;Baron and Woods 1995;Grant et al 1996;Zajaczkowski et al 1996;Wiley et al 1997;Witkin et al 1997;Helsley et al 1998;Medvedev et al 1998;). These findings indicate that NMDA receptor antagonists do not produce a common interoceptive cue that would lead to a common state-dependent effect masquerading as an inhibition of tolerance.…”

Section: Nmda Receptor Antagonists and The Development Of Tolerance Tmentioning

confidence: 94%

Are NMDA receptors involved in opiate-induced neural and behavioral plasticity?

2000

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NMDA receptor antagonists appear to inhibit the neural plasticity underlying some forms of opiate tolerance, sensitization and physical dependence, suggesting that NMDA receptors are involved in the development of these drug-induced changes in behavior. Further research will help to determine the neural mechanisms responsible for these phenomena, and the therapeutic potential for drugs acting on the NMDA receptor complex in the treatment of pain and addiction.

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“…For example, any of a number of GABA-positive modulators and NMDA antagonists will completely substitute in animals trained to discriminate ethanol from vehicle (De Vry and Slangen 1986;Kostowski and Bienkowski 1999;Shelton and Grant 2002). However, when ethanol is tested in animals trained to discriminate those same GABA positive modulators or NMDA antagonists from vehicle, ethanol produces little if any substitution (Balster et al 1992;Butelman et al 1993;De Vry and Slangen 1986;Herling et al 1980). This unique pattern of results has been termed asymmetric or asymmetrical substitution.…”

Section: Introductionmentioning

confidence: 99%

Inhaled toluene vapor as a discriminative stimulus

Shelton

2007

Behavioural Pharmacology

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Objectives-There have been few studies exploring the discriminative stimulus effects of inhalants and none that have trained an interoceptive discrimination using the inhaled route. This study was designed to assess if it was possible to train an inhaled toluene discrimination. The second objective was to determine whether the discrimination was based on interoceptive or exteroceptive stimulus effects.Methods-Eight B6SJLF1/J mice were trained to discriminate 10 min of exposure to 6000 ppm inhaled toluene vapor from air using a standard food-reinforced operant procedure.Results-Toluene vapor produced robust, concentration dependent, discriminative stimulus effects with concentrations of 4000 ppm and higher producing full substitution. Substitution of inhaled toluene vapor for the training condition was exposure-time dependent. A minimum of 7 min of exposure to 6000 ppm was required to produce complete substitution. Injected i.p. toluene produced dose-dependent full substitution for inhaled toluene vapor. Both inhaled and i.p. ethylbenzene produced similar levels of partial substitution for 6000 ppm toluene vapor. Inhaled isoflurane vapor produced no substitution for toluene vapor.Conclusions-These results show that a toluene vapor discrimination can be successfully trained in mice and the discrimination is selective for toluene compared to ethylbenzene and isoflurane. The results also suggest that the discrimination was likely to have been based primarily on interoceptive rather than exteroceptive stimulus effects.

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Drug discrimination analysis of ethanol as an N-methyl-D-aspartate receptor antagonist

Cited by 30 publications

References 16 publications

Ethanol and N -methyl- D -aspartate receptor complex interactions: a detailed drug discrimination study in the rat

Ethanol and N -methyl- D -aspartate receptor complex interactions: a detailed drug discrimination study in the rat

Are NMDA receptors involved in opiate-induced neural and behavioral plasticity?

Inhaled toluene vapor as a discriminative stimulus

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