Effects of acute inhalation exposure to 1,1,1-trichloroethane on the hypothalamo-pituitary-adrenal axis in male Sprague-Dawley rats.
1,1,1-Trichloroethane (TRI) is a commonly used industrial solvent with a considerable potential for inhalation abuse. Previous studies in our laboratory and elsewhere have shown that this agent exerts a suppressant effect on operant responding, as well as a number of additional neurobehavioral effects that are similar to those of central nervous system (CNS) depressant drugs. In an effort to provide information relevant to potential mechanisms involved in the behavioral effects and abuse potential of TRI, the present study evaluated the acute effects of this agent on the activity of the hypothalamo-pituitary-adrenal (HPA) axis . Male Sprague-Dawley rats were exposed to 3500 or 5000 ppm TRI by inhalation for 10 or 30 min. Following exposure, plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone and levels of ACTH and corticotropin-releasing factor (CRF) in three brain regions--hypothalamus, hippocampus, and frontal cortex--were determined by selective radioimmunoassays. Levels of TRI in the three brain regions as well as blood were measured by headspace gas chromatography to determine the target tissue concentrations responsible for neuroendocrine changes. Uptake of TRI in blood and all brain regions was very rapid, with stable concentrations apparently achieved within 10 min and maintained for 30 min. During this time course, a significant decrease in plasma corticosterone was produced at 30 min but no significant change in plasma ACTH was observed with 3500 ppm TRI. However, after exposure to 5000 ppm, both plasma ACTH and plasma corticosterone were significantly reduced at 10 and 30 min. ACTH levels in the three brain regions were not significantly changed by TRI, while hypothalamic CRF was significantly increased during exposure to 3500 ppm. However, hypothalamic concentrations of CRF declined following 30 min at 3500 ppm and were not significantly changed by 5000 ppm. This complexity of effects on the regulation of HPA axis activity likely precluded the establishment of consistent relationships between changes in hormonal levels and blood or regional brain concentrations of the inhalant. However, these actions of TRI were strikingly similar to those previously reported for the benzodiazepines.
Pise
V M
VM
Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602-2356, USA.
Reigle
T G
TG
Muralidhara
S
S
Dallas
C E
CE
D000280:Administration, Inhalation; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D014240:Trichloroethanes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D007457:Iodine Radioisotopes; D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone