STRESS-INDUCED CROSS-SENSITIZATION TO COCAINE - EFFECT OF ADRENALECTOMY AND CORTICOSTERONE AFTER SHORT-TERM AND LONG-TERM WITHDRAWAL

We have recently shown that adrenalectomy (ADX) in rats blocks the app earance of cocaine-induced sensitization when this behavioral response is tested at early withdrawal times (1-2 days), but not after later w ithdrawal from cocaine (12 days), To determine if a similar phenomenon occurred with stress-induced sensitization, male Sprague-Dawley rats were given a sham ADX, ADX surgery, or ADX plus SC implanted corticost erone (CORT) pellets (CORT 12.5% pellets or CORT 50% pellets). A fifth group was given ADX surgery, but CORT 50% pellets were implanted afte r repeated stress treatment. One week after surgery, each group was di vided into two additional groups, naive and stress. Naive animals rema ined unhandled, while stress rats were given a variety of daily stress ors administered twice per day for 6 consecutive days. One day after t he last stress, rats were given a saline injection followed by a cocai ne injection (15 mg/kg, IF) the next day, and locomotor activity was m onitored (early withdrawal!. Two weeks after the last stress, the loco motor responses to an additional saline and cocaine injection were mon itored (late withdrawal). At early withdrawal, no significant sensitiz ation occurred for horizontal activity, but cross-sensitization was de monstrated for vertical activity. At late withdrawal, sham controls sh owed a stress-induced elevation in horizontal activity, with only a tr end toward increased vertical activity. Animals given ADX surgery or A DX and CORT 12.5% pellets did not demonstrate sensitization to repeate d stress, while CORT 50% pellets in ADX rats restored the sensitized h orizontal response to cocaine challenge at late withdrawal. In contras t, stress-pretreated rats which were given CORT 50% pellets during the 2-week withdrawal period after the stress showed a marked decrease in horizontal activity in response to cocaine challenge at late withdraw al. The results provide evidence for a necessary role for adrenal horm ones in long term, but not short-term, stress-induced cross-sensitizat ion. Together with our previous study on the role of CORT in cocaine-i nduced sensitization, the results indicate that CORT is not the common factor mediating the long-term sensitization to cocaine and stress.