Abstract
The effect of electrolytic lesions in the median and dorsal raphe nuclei was tested on acute tolerance development to ethanol and pentobarbital in the rat, as measured by motor impairment on the moving belt test. Acute tolerance to ethanol (1.7 g/kg, IP) or pentobarbital (17.5 mg/kg, IP) was monitored at 12.5, 25, or 50 min in separate subgroups tested only once each. One week of recovery was allowed between ethanol and pentobarbital tests. Median raphe lesions delayed the development of acute tolerance, whereas dorsal raphe lesions produced a negligible effect. These results were seen with both ethanol and pentobarbital. The mesolimbic 5-HT pathway from the median raphe nucleus is important in the development of acute tolerance to ethanol and pentobarbital, as was shown to be the case previously for chronic tolerance.
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References
Gibbins RJ, Kalant H, LeBlanc AE (1968) A technique for accurate measurement of moderate degrees of alcohol intoxication in small animals. J Pharmacol Exp Ther 159:236–242
Hawkins RD, Kalant H, Khanna JM (1966) Effect of chronic intake of ethanol on rate of ethanol metabolism. Can J Physiol Pharmacol 44:241–257
Jones BM, Vega A (1972) Cognitive performance measured on the ascending and descending limb of the blood alcohol curve. Psychopharmacologia 23:99–114
Kalant H, Khanna JM (1986) Metabolic and functional aspects of tolerance to chlormethiazole and cross-tolerance to ethanol in rat. Acta Psychiatr Scand [Suppl 329] 73:45–53
Kalant H, LeBlanc AE, Gibbins RJ (1971) Tolerance to, and dependence on, some non-opiate psychotropic drugs. Pharmacol Rev 23:135–191
Kalant H, LeBlanc AE, Gibbins RJ, Wilson A (1978) Acceleration of development of tolerance during repeated cycles of ethanol exposure. Psychopharmacology 60:59–65
Khanna JM, Lê AD, Kalant H, Kim C (1985) Differential sensitivity to ethanol, pentobarbital, and barbital in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Psychopharmacology 86:296–301
Khanna JM, Campanelli C, Lê AD, Kalant H (1987) Effect of raphe lesions on the development of chronic tolerance to pentobarbital and cross-tolerance to ethanol. Psychopharmacology 91:473–478
Lê AD, Khanna JM, Kalant H, LeBlanc AE (1981a) The effect of lesions in the dorsal, median and magnus raphe nuclei on the development of tolerance to ethanol. J Pharmacol Exp Ther 218:525–529
Lê AD, Khanna JM, Kalant H, LeBlanc AE (1981b) Effect of modification of brain serotonin (5-HT), norepinephrine (NE) and dopamine (DA) on ethanol tolerance. Psychopharmacology 75:231–235
LeBlanc AE, Kalant H, Gibbins RJ, Berman ND (1969) Acquisition and loss of tolerance to ethanol by the rat. J Pharmacol Exp Ther 168:244–250
LeBlanc AE, Kalant H, Gibbins RJ (1975) Acute tolerance to ethanol in the rat. Psychopharmacologia 41:43–46
Littleton JM (1980) The assessment of rapid tolerance to ethanol. In: Rigter R, Crabbe JC Jr (eds) Alcohol tolerance and dependence. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 53–79
Maynert EW, Klingman GI (1960) Acute tolerance to intravenous anesthetics in dogs. J Pharmacol Exp Ther 128:192–200
Mellanby E (1919) Alcohol: its absorption into and disappearance from the blood under different conditions. Special Report Series no 31, Medical Research Committee, London
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Campanelli, C., Lê Dzung, A., Khanna, J.M. et al. Effect of raphe lesions on the development of acute tolerance to ethanol and pentobarbital. Psychopharmacology 96, 454–457 (1988). https://doi.org/10.1007/BF02180023
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DOI: https://doi.org/10.1007/BF02180023