Alcohol, Vol. 2, pp. 655-658. 1985. ~ AnkhoInternational Inc. Printed in the U.S.A. 0741-8329/85$3.00 + .00 A Comparison of Ethanol Absorption and Narcosis in Long- and Short-Sleep Mice Following Intraperitoneal or Intragastric Ethanol Administration DAVID M. GILLIAM, TAMARA J. PHILLIPS AND BRUCE C. DUDEK 1 Department of Psychology and the Neurobiology Research Center, State University of New York at Albany 1400 Washington Avenue, Albany, NY 12222 Received 15 February 1985 GILLIAM, D. M., T. J. PHILLIPS AND B. C. DUDEK. A comparison of ethanol absorption and narcosis in Long- and Short-Sleep mice fidlowing intraperitoneal or intragastric ethanol administration. ALCOHOL 2(5) 655---658, 1985.--Blood ethanol concentrations (BEC) were determined in Long-Sleep (LS) and Short-Sleep (SS) mice during a 30 rain period following ethanol {ETOH) administration. Absorption of ETOH was rapid and followed a similar time course in the two lines after intraperitoneal (IP) administration of 3.8 or 4.5 g/kg. Following intragastric fiG) administration, slower absorp- tion and lower peak BECs were noted in both lines, but in LS mice this effect was more pronounced. The two routes of administration were not effective in altering duration of loss of the righting reflex (LRR), or waking BECs following 4.5 g/kg ETOH. LS mice had the expected longer LRR durations and lower BECs at waking than did SS mice. Differences in absorption rate and peak BEC are concluded to be unrelated to ETOH neurosensitivity in these mice. Ethanol Pharmacogenetics Long- and Short-Sleep mice Ethanol Absorption Route of administration ROUTE of psychotropic drug administration is known to affect behavioral response both qualitatively and quantita- tively [21]. In studies of the behavioral pharmacology of ethanol (ETOH), this factor is assumed to exert its influence simply by altering blood ethanol concentrations (BEC). However, initial sensitivity and acute tolerance may depend, in part, on absorption rate [4, 17, 20, 23]. In the studies reported here, we manipulated route of ETOH administra- tion (and indirectly, absorption rate) in genetically defined lines of mice and assessed its importance for observed sen- sitivity differences. Studies of genetically-based differences in ETOH sensi- tivity indicate that both dispositional and tissue sensitivity fac- tors can influence response [!,4]. The selectively bred Long-Sleep tLS) and Short-Sleep (SS) mice are known to differ in neurosensitivity to ETOH [28]. Differences in rate of ETOH clearance during the linear portion of the elimina- tion curve are not thought to be important for the differences in behavioral sensitivity of these two lines [18,24]. How- ever, CNS differences may not completely explain the suc- cess of the selection for the narcosis phenotype. Effects of ETOH on peripheral physiology [13] and demonstration of concentration-dependent ETOH effects in these two lines [ 14,15] suggest the possibility that the administration of ETOH intraperitoneally (1P), may result in effects on periph- eral tissues. This, in turn, may produce some of the behav- ioral differences seen between the lines. An hypothesis has ~Requests for reprints should be addressed to B. C. Dudek. been generated stating that the LS/SS sensitivity difference may partially depend on ETOH effects produced by the specific route of administration [14]. One aspect of these issues that has not received examina- tion is the time course of BECs immediately following ETOH administration. Several studies of ETOH elimination in the LS and SS lines have focused on clearance of ETOH after it reaches its peak levels [16, 18, 24, 27]. It is possible that differences in absorption rates exist between the lines, and that some of the differences in behavioral response may result from this. Many of the studies of behavioral effects of ETOH in LS and SS mice used a protocol which involved testing the mice shortly after ETOH administration [2, 5-9, 26]. Examination of absorption rate is thus indicated. We report here, two studies which address these is- sues. The first directly examined BECs immediately after either IP or IG ETOH administration at two doses. The 3.8 g/kg dose is the dose studied in genetic analyses of the selec- tion phenotype, duration of the loss of the righting reflex (LRR) [6]. A second dose (4.5 g/kg) was chosen because of its use in the second experiment reported here. This second experiment indirectly manipulated the profile of BEC con- centrations following ETOH administration by varying route of administration. Duration of LRR and BEC at waking were measured in mice treated either IP or 1G. The expectation was that if rate of ETOH absorption or peak BECs were influential in the degree of narcosis or acute tolerance devel- 655