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• 1. [Article] Thermoregulation in Mice under the Influence of Ethanol

  Thermoregulation after acute ethanol, during chronic exposure and during withdrawal from ethanol dependency was studied using genetically heterogeneous (HS) mice, and lines of mice selected in replicate ...

  Citation × Citation Citation Abstract Copy Title: Thermoregulation in Mice under the Influence of Ethanol Author: O'Connor, Candace Sharon Year: 1993 Thermoregulation after acute ethanol, during chronic exposure and during withdrawal from ethanol dependency was studied using genetically heterogeneous (HS) mice, and lines of mice selected in replicate for smaller (HOT1, HOT2) or greater (COLD1, COLD2) decline in rectal temperature (Tre ) after intraperitoneal ethanol. First, HS mice were injected with 20% ethanol in 0.9% NaCI, or NaCI alone during sessions of behavioral thermoregulation in individual temperature gradients (9-38°C). Internal temperature (Tj ) was monitored with implanted telemetry devices. An imaging system recorded selected temperature (Tsel ) within the gradient every 5 sec. Acute 2.25 and 2.60 g ethanol/kg produced significantly lower Tj than NaCI. 2.60 g/kg also produced significantly lower Tsel than 2.25 g/kg or NaCI. 2.75 g/kg and above incapacitated mice. Comparison of responses using a thermoregulatory index indicated 2.25 or 2.60 g/kg decreased the regulated temperature. Similar methodology was followed using the selected lines and 10% ethanol (2.0, 2.25, 2.65 g/kg to COLD mice; 2.65, 2.85 g/kg to HOT mice; 3.0 g/kg to HOT2 mice) or NaCI. All responded similarly to NaCl, with transient rise in Tj After an effective ethanol dose mice manifested a regulated decrease in Tj by lowering Tsel concomitant with falling Tj . In both replicate pairs COLD mice were more sensitive than HOT, indicating that a true difference in the CNS regulator of body temperature was selected for in these animals. Photoperiod effect was characterized by quantifying thermoregulatory behavior of COLD2 mice after acute 2.60 g 7.5% ethanol/kg or NaCl, at 0400 , 0800 , 1200, 1600 , 2000 and 2400 hours , using above methodology. Baseline T₁ was significantly lower during hours of light, than during darkness. Photoperiod had little effect on thermoregulatory response to ethanol, possibly because of arousal associated with experiments. Thermoregulatory tolerance to ethanol was investigated using HS mice implanted with telemetry devices and monitored in the gradient on days 1, 2, 4, 7 and 11 of 11 consecutive days of 10% ethanol (2.75 g/kg) or NaCl injections. Dispositional, rapid and chronic tolerance developed, indicating that functional tolerance is a regulated phenomenon in mice. In a separate experiment HS mice were implanted with telemetry devices and injected with ethanol for 11 consecutive days at constant temperature; dispositional but not functional tolerance developed. To characterize thermoregulation during withdrawal, HS mice were made dependent upon ethanol using a vapor chamber; T; Tsel and activity were monitored in the gradient until 26 hours post withdrawal. Withdrawing mice showed unaltered regulated temperature, but lower Tsel than controls. This suggested increased metabolic heat production. Thermoregulation during withdrawal was similarly studied using the selected mouse lines. COLD mice responded like HS mice. Withdrawing HOT1 mice were more active than controls; withdrawing HOT2 mice showed lowest Tsel of any genotype but maintained Ti above controls. These results suggest a more severe withdrawal reaction in HOT, than in COLD mice. To investigate a possible mechanism underlying ethanol hypothermia, responses of HOT and COLD mice to intracerebroventricular serotonin were characterized. Dose-dependent decreases in Tre were measured in mice equipped with indwelling brain cannulae and held at constant temperature after injection of 0.3, 0.8, 2.0, 5.0 or 11.0 μg serotonin into the lateral brain ventricle. COLD mice were significantly more sensitive than HOT mice. Subsequently HOT1 and COLD1 mice were equipped with brain cannulae and implanted telemetry devices; thermoregulatory behavior after 11.0 μg serotonin was monitored. Both genotypes lowered Tj significantly more in the gradient than did similar mice at constant ambient temperature, indicating that decline in Tj after serotonin was a regulated phenomenon. The serotonergic system was altered during selection for differential Tre response to ethanol, indicating a role for serotonin in mediating ethanol hypothermia. Title: Thermoregulation in Mice under the Influence of Ethanol Author: O'Connor, Candace Sharon Year: 1993 Thermoregulation after acute ethanol, during chronic exposure and during withdrawal from ethanol dependency was studied using genetically heterogeneous (HS) mice, and lines of mice selected in replicate for smaller (HOT1, HOT2) or greater (COLD1, COLD2) decline in rectal temperature (Tre ) after intraperitoneal ethanol. First, HS mice were injected with 20% ethanol in 0.9% NaCI, or NaCI alone during sessions of behavioral thermoregulation in individual temperature gradients (9-38°C). Internal temperature (Tj ) was monitored with implanted telemetry devices. An imaging system recorded selected temperature (Tsel ) within the gradient every 5 sec. Acute 2.25 and 2.60 g ethanol/kg produced significantly lower Tj than NaCI. 2.60 g/kg also produced significantly lower Tsel than 2.25 g/kg or NaCI. 2.75 g/kg and above incapacitated mice. Comparison of responses using a thermoregulatory index indicated 2.25 or 2.60 g/kg decreased the regulated temperature. Similar methodology was followed using the selected lines and 10% ethanol (2.0, 2.25, 2.65 g/kg to COLD mice; 2.65, 2.85 g/kg to HOT mice; 3.0 g/kg to HOT2 mice) or NaCI. All responded similarly to NaCl, with transient rise in Tj After an effective ethanol dose mice manifested a regulated decrease in Tj by lowering Tsel concomitant with falling Tj . In both replicate pairs COLD mice were more sensitive than HOT, indicating that a true difference in the CNS regulator of body temperature was selected for in these animals. Photoperiod effect was characterized by quantifying thermoregulatory behavior of COLD2 mice after acute 2.60 g 7.5% ethanol/kg or NaCl, at 0400 , 0800 , 1200, 1600 , 2000 and 2400 hours , using above methodology. Baseline T₁ was significantly lower during hours of light, than during darkness. Photoperiod had little effect on thermoregulatory response to ethanol, possibly because of arousal associated with experiments. Thermoregulatory tolerance to ethanol was investigated using HS mice implanted with telemetry devices and monitored in the gradient on days 1, 2, 4, 7 and 11 of 11 consecutive days of 10% ethanol (2.75 g/kg) or NaCl injections. Dispositional, rapid and chronic tolerance developed, indicating that functional tolerance is a regulated phenomenon in mice. In a separate experiment HS mice were implanted with telemetry devices and injected with ethanol for 11 consecutive days at constant temperature; dispositional but not functional tolerance developed. To characterize thermoregulation during withdrawal, HS mice were made dependent upon ethanol using a vapor chamber; T; Tsel and activity were monitored in the gradient until 26 hours post withdrawal. Withdrawing mice showed unaltered regulated temperature, but lower Tsel than controls. This suggested increased metabolic heat production. Thermoregulation during withdrawal was similarly studied using the selected mouse lines. COLD mice responded like HS mice. Withdrawing HOT1 mice were more active than controls; withdrawing HOT2 mice showed lowest Tsel of any genotype but maintained Ti above controls. These results suggest a more severe withdrawal reaction in HOT, than in COLD mice. To investigate a possible mechanism underlying ethanol hypothermia, responses of HOT and COLD mice to intracerebroventricular serotonin were characterized. Dose-dependent decreases in Tre were measured in mice equipped with indwelling brain cannulae and held at constant temperature after injection of 0.3, 0.8, 2.0, 5.0 or 11.0 μg serotonin into the lateral brain ventricle. COLD mice were significantly more sensitive than HOT mice. Subsequently HOT1 and COLD1 mice were equipped with brain cannulae and implanted telemetry devices; thermoregulatory behavior after 11.0 μg serotonin was monitored. Both genotypes lowered Tj significantly more in the gradient than did similar mice at constant ambient temperature, indicating that decline in Tj after serotonin was a regulated phenomenon. The serotonergic system was altered during selection for differential Tre response to ethanol, indicating a role for serotonin in mediating ethanol hypothermia. Close