Influence of thyrotropin-releasing hormone and catecholaminergic interactions on CNS ethanol sensitivity.
The role of catecholamine neuronal systems in mediating the analeptic and thermogenic effects of thyrotropin-releasing hormone (TRH) was examined in long-sleep (LS) and short-sleep (SS) mice. TRH [0.1 to 40 micrograms, intracerebroventricularly (icv)] was associated with a reduction in the sleep times of LS mice, but no dose of TRH had any effect on sleep times of SS mice. However, TRH (20 micrograms, icv) produced a 1.0 degree to 1.5 degrees C attenuation of the ethanol-induced hypothermia in both LS and SS mice. TRH did not change the rate of ethanol elimination in either line of mice, suggesting that the reduction in LS sleep times and attenuation of LS and SS hypothermia were due to decreased CNS ethanol sensitivity rather than an increase in the rate of ethanol metabolism. TRH (20 micrograms, icv) given alone produced an activation of central and peripheral catecholamine systems in LS, but not SS mice, as reflected by an increase in the in vivo tyrosine hydroxylase (TH) activity in the brain and adrenal gland. TRH, given with ethanol, prevented or attenuated ethanol-induced decreases in the brain and adrenal gland in vivo TH activity in LS mice but not SS mice. Thus, there was an association between the ability of TRH to produce an activation of catecholamine neuronal systems (increased rate of catecholamine biosynthesis) and the analeptic action of TRH to reduce the CNS depressant effects of ethanol (decreased sleep times).(ABSTRACT TRUNCATED AT 250 WORDS)
French
T A
TA
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Masserano
J M
JM
Weiner
N
N
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D002395:Catecholamines / Q000502:physiology*; D000431:Ethanol / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000502:physiology; D012894:Sleep Stages / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000502:physiology
D002395:Catecholamines; D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase