Dopamine receptors mediate cocaine-induced temperature responses in spontaneously hypertensive and Wistar-Kyoto rats.
The involvement of dopaminergic receptors in the responses of conscious, restrained spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats to cocaine was examined using antagonists selective for DA-1 (SCH 23390) or DA-2 (sulpiride) dopamine receptors. Following pretreatment with saline vehicle, SCH 23390 (50 mg/kg, SC), sulpiride (50 mg/kg, IP) or SCH 23390 and sulpiride, cocaine was infused (1.25 mg/kg.min, IV) until death. Cocaine caused an initial pressor and tachycardiac response, which was followed by a progressively developing secondary pressor response. Combined (DA-1 and DA-2) antagonist pretreatment abolished the initial tachycardic response to cocaine. Rectal temperature during cocaine infusion increased in 38.5% of vehicle-treated SHR (designated SHRH), but decreased in the remaining SHR (SHRL) and all vehicle-treated WKY. The time-to-onset of cocaine-induced convulsions (Tc) was reduced in vehicle-treated SHRH compared to vehicle-treated SHRL and WKY. Sulpiride elevated rectal temperature in response to cocaine in SHR and WKY but reduced Tc only in SHR. SCH 23390 abolished hyperthermic responses to cocaine in SHR without altering toxicity in SHR or WKY. Combined pretreatment virtually abolished temperature responses to cocaine in SHR and WKY, but increased the Tc only in WKY. Dopamine receptors, particularly the DA-1 subtype, are involved in cocaine-induced hyperthermia.
Rockhold
R W
RW
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Carver
E S
ES
Ishizuka
Y
Y
Hoskins
B
B
Ho
I K
IK
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D003042:Cocaine