Postcocaine anhedonia. An animal model of cocaine withdrawal.
Cocaine use frequently occurs in episodic, prolonged binges. Following such a cocaine binge, the user suffers from severe depressive symptoms mixed with irritability and anxiety ("crash"). The present study was an attempt to develop an animal model of postcocaine depression or anhedonia and to study the time course of this cocaine withdrawal symptom. Rats were allowed to self-administer cocaine intravenously for prolonged periods of time and their brain reward thresholds were then assessed using intracranial self-stimulation (ICSS) thresholds. ICSS thresholds were used operationally as a measure of the animals' "hedonic-anhedonic" state. It was found that during cocaine withdrawal ICSS thresholds were elevated compared to predrug baseline levels and to control animals' thresholds, reflecting an "anhedonic" state. The magnitude and duration of the "anhedonic" state was proportional to the amount of cocaine consumed during the binge. A measure of response latency provided evidence that this postcocaine elevation of thresholds is due to a desensitization of the reward pathways mediating ICSS reward and not to any nonspecific (e.g., performance) effects of the cocaine exposure.
Markou
A
A
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Koob
G F
GF
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D012653:Self Stimulation; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology
D003042:Cocaine