Behavioral and brain temperature responses to salient environmental stimuli and intravenous cocaine in rats: effects of diazepam.
BACKGROUND
While diazepam is an effective anxiolytic and somnolent drug in humans, its physiological and behavioral effects in animals are often variable. Differences in basal activity state (basal arousal) may be important in determining both this response variability and the pattern of drug influence on behavioral and physiological responses to natural arousing stimuli and other drugs.


OBJECTIVE
To evaluate the changes in brain, muscle, and skin temperatures, and in locomotion induced in rats by several arousing stimuli and intravenous (i.v.) cocaine; and to assess how these responses are modulated by diazepam at a relatively low dose (1 mg/kg, i.p.).


METHODS
Male rats were implanted with thermal probes in the nucleus accumbens (NAcc), temporal muscle, and subcutaneously, and equipped with a chronic i.v. catheter. They were exposed to 1-min tail-pinch, 1-min social interaction with another male and cocaine (1 mg/kg, i.v.) after administration of diazepam or saline.


RESULTS
While the injection of either diazepam or saline resulted in similar locomotor activation and temperature responses, diazepam decreased basal brain and muscle temperatures for about 3 h; the temperature-decreasing effect of diazepam was oppositely related to basal brain temperature (r = -0.51). After diazepam, rats also showed weaker temperature and locomotor responses to both arousing stimuli; the effect was stronger for tail-pinch and for absolute temperature increases than relative changes. Although diazepam significantly decreased cocaine-induced locomotor activation, it had virtually no effects on cocaine-induced temperature responses in all locations.


CONCLUSIONS
In accordance with the "law of initial values", the temperature-increasing effects of all tested arousing stimuli and temperature-decreasing effect of diazepam depend upon basal brain temperature. The greatest temperature effects are seen with arousing stimuli at low basal arousal (increases) and with diazepam at high basal arousal (decreases). This is a likely explanation for the variability seen with the physiological and behavioral effects of diazepam in animals.
Kiyatkin
Eugene A
EA
National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, 21224, MD, USA. ekiyatki@intra.nida.nih.gov
Bae
David
D
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D014151:Anti-Anxiety Agents; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D003975:Diazepam