The long term objectives of this research are to understand the mechanism whereby ethanol affects temperature regulation, and to utilize this understanding to clarify the myriad effects that occur when biological systems encounter ethanol. The thermoregulatory system is an appropriate choice for study because (1) Victims of hypothermia (outdoors) and hyperthermia (hot tubs) are often intoxicated with ethanol (2) The hypothermia that usually follows moderate and high levels of alcohol intake produces many secondary effects on other physiological and biochemical systems of the body (3) Alcohol hypothermia in rodents has been widely used as a model system to study the effects of ethanol. Behavioral thermoregulatory responses are emphasized in this study of temperature regulation because these responses allow the animal to compensate for disruptions in effector mechanisms; study of behavior therefore directly focuses on central nervous system effects. Mice are utilized because (1) genetically selected lines are available which have a differential thermal response to ethanol; and (2) in mice, temperature selection as well as core body temperature can be continuously monitored in a thermal gradient. Goldfish are also utilized because these vertebrates are cold blooded and thus are limited to behavioral means of regulating their body temperature. The proposed experiments are broken into two parts. In the first part, experiments will be performed (on both species) to establish the effect of ethanol on temperature regulation during, and under changes in a variety of conditions--time of photoperiod, acute tolerance, chronic tolerance and withdrawal. The basic response of the different genetic lines of mice will also be evaluated. In the second part, information obtained from the first part will be utilized in experiments designed to elucidate the central nervous mechanism of ethanol-induced hypothermia. In mice, the site of hypothalamic thermosensitivity will be accurately localized, and the responsiveness to intrahypothalamic injections of ethanol and neurotransmitters will be compared for the alcohol sensitivity and alcohol insensitive genetic lines of mice. In goldfish, attempts will be made to link the effects of ethanol to specific neurotransmitter systems.
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| Crawshaw, L I; O'Connor, C S; Crabbe, J C et al. (1994) Temperature regulation in mice during withdrawal from ethanol dependence. Am J Physiol 267:R929-34 |
| O'Connor, C S; Crawshaw, L I; Crabbe, J C (1993) Genetic selection alters thermoregulatory response to ethanol. Pharmacol Biochem Behav 44:501-8 |
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| Crawshaw, L I; Wollmuth, L P (1992) Effective loci and roles of acetylcholine in temperature regulation of goldfish. Am J Physiol 263:R596-601 |
| O'Connor, C S; Crawshaw, L I; Kosobud, A et al. (1989) The effect of ethanol on behavioral temperature regulation in mice. Pharmacol Biochem Behav 33:315-9 |
