PHYSIOLOGICAL AND SUBJECTIVE EFFECTS OF ACUTE COCAINE WITHDRAWAL (CRASH) IN RATS

The physiological and subjective effects of high acute doses of cocain e and the subsequent homeostatic acute withdrawal syndrome were measur ed in rats. Radiotelemetry recordings of body temperature and activity were monitored in rats for 48 h after 32 mg/kg cocaine (COG) and sali ne (SAL) were administered by both intraperitoneal and subcutaneous (S C) routes. COC initially produced hypothermia and hyperactivity, follo wed by a prolonged hyperthermic and hypoactive rebound that seemed to peak around 12 h after injections. The SC route of administration prod uced the greatest rebound effect. Eight additional rats were monitored for EEG activity by telemetry for 48 h after SC administration of SAL or 32 mg/kg COG. COC produced an initial decrease in alpha and beta w avelength bands, with a trend toward increases in alpha and beta power demonstrated from the 10th through 14th h after injections. Using a t hree-choice haloperidol (HDL), saline, and COC drug discrimination tas k, we demonstrated a COG-like subjective state produced during the 10t h through 12th h after a 32-mg/kg SC COC injection with no HDL-like re sponding engendered during any tested period of the acute or rebound e ffects of COG. These data provide evidence for an acute COC withdrawal syndrome (crash) in rats occurring 10-14 h after a high-dose COC trea tment. (C) 1997 Elsevier Science Inc.