Effects of abused inhalants and GABA-positive modulators in dizocilpine discriminating inbred mice.
There is in vitro evidence that some of the effects of abused volatile solvents may be produced by actions at the NMDA receptor. In addition, some solvents produce phencyclidine-like discriminative stimulus effects. The major goal of the present study was to further compare abused solvents to NMDA antagonists by testing them in two strains of mice trained to discriminate 0.17 mg/kg of the very selective uncompetitive NMDA antagonist, dizocilpine, from saline and contrast those results with several GABA(A)-positive modulators, PCP and ethanol. The results indicated that the discriminative stimulus produced by 0.17 mg/kg dizocilpine was highly specific in both mouse strains. PCP produced 91% dizocilpine-lever responding in C57BL/6J mice, but only 56% dizocilpine-lever responding in DBA/2J mice. Pentobarbital, midazolam and ethanol produced at least some overlap in discriminative stimulus effects with dizocilpine in one or both mouse strains. In contrast, toluene, 1,1,1-trichloroethane (TCE), xylene and methoxyflurane produced saline-appropriate responding almost exclusively. These data indicate that, at least under the specific conditions tested, abused volatile solvents do not have substantial dizocilpine-like discriminative stimulus effects in either C57BL/6J or DBA/2J mice, providing little support that NMDA antagonism plays a central role in the production of this abuse-related effect.
Shelton
Keith L
KL
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, P.O. Box 980613, Richmond, VA 23298-0613, USA. klshelto@hsc.vcu.edu
Balster
Robert L
RL
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D013287:Illicit Drugs / Q000633:toxicity*; D008733:Methoxyflurane / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008874:Midazolam / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012997:Solvents / Q000633:toxicity; D014050:Toluene / Q000633:toxicity; D014240:Trichloroethanes / Q000633:toxicity; D014992:Xylenes / Q000633:toxicity
D018757:GABA Modulators; D013287:Illicit Drugs; D016194:Receptors, N-Methyl-D-Aspartate; D012997:Solvents; D014240:Trichloroethanes; D014992:Xylenes; C024566:1,1,1-trichloroethane; D008733:Methoxyflurane; D014050:Toluene; D016291:Dizocilpine Maleate; D010424:Pentobarbital; D010622:Phencyclidine; D008874:Midazolam