Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration "binges".
BACKGROUND
Repeated social stress experiences engender "behavioral sensitization" and may also increase the potential for abuse of psychomotor stimulants, particularly cocaine use during "binges."


OBJECTIVE
Experimental protocols were designed to induce behavioral sensitization through exposures to social-defeat stress or injections of cocaine or morphine. The impact of stress, cocaine or morphine sensitization on cocaine self-administration was assessed using several protocols.


METHODS
Behavioral sensitization was induced in male Long-Evans rats by four social-defeat stress episodes, each separated by 72 h. Expression was assessed following a challenge of D-amphetamine (1.0 mg/kg) or cocaine (7.5 mg/kg or 10.0 mg/kg), 10-15 days after the last defeat. Sensitization to cocaine (15.0 mg/kg) or morphine (10.0 mg/kg) was induced via daily administrations for 10 days and later assessed by challenges with cocaine or morphine. Subsequently, i.v. self-administration of cocaine was analyzed for (i) rates of acquisition, (ii) sensitivity to various doses, (iii) "breaking points" during a progressive ratio schedule of cocaine reinforcement, and (iv) patterns of intake during a 24-h binge, in sensitized and control rats.


RESULTS
Social-defeat stress, cocaine or morphine administrations increased the locomotor response to stimulant challenges. During 24-h cocaine self-administration binges, sensitization to social-defeat stress or to cocaine prolonged responding, resulting in more cocaine intake. In addition, cocaine sensitization increased the rate of acquisition to cocaine self-administration and the breaking point during a progressive ratio schedule.


CONCLUSIONS
The process of sensitization to social-defeat stress or cocaine intensifies cocaine intake during a binge, supporting the hypothesis that sensitization may facilitate the transition to compulsive drug taking.
Covington
H E
HE
Department of Psychology, Tufts University, Bacon Hall, 530 Boston Avenue, Medford, MA 02155, USA.
Miczek
K A
KA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003345:Corticosterone / Q000097:blood; D003913:Dextroamphetamine / Q000494:pharmacology; D004291:Dominance-Subordination; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D013315:Stress, Psychological / Q000523:psychology*
D000697:Central Nervous System Stimulants; D009294:Narcotics; D009020:Morphine; D003042:Cocaine; D003913:Dextroamphetamine; D003345:Corticosterone