A rodent model of cocaine abstinence syndrome.
This study introduces a rat model of cocaine abstinence syndrome based on quantitation of spontaneously emitted behaviors following termination of continuous drug exposure (analogous to established methods of assessing morphine and nicotine abstinence). Groups of eight male S-D rats were infused SC for 7 days via an osmotic minipump with saline alone or with 40 or 60 mg/kg/day cocaine HCl. Pumps were removed and rats were observed at 12, 24, 36, and 48 h postremoval. Each 15-min observation employed a checklist of abstinence signs including ptosis, chews, teeth chatters, gasps, writhes, seminal ejaculations, head shakes, and tremors. The high infusion rate group displayed significantly more signs than the low infusion rate group, which in turn, displayed significantly more signs than the saline group. Cocaine injection significantly reduced signs by 83.3%, while saline injection reduced them by only 4.9%. In another experiment, rats infused with 60 mg/kg/day showed significantly more signs 36 h postinfusion than before infusion, during infusion and 84 h postinfusion. Finally, 6.5 days of infusion resulted in significantly more abstinence signs than did 1.5 days of infusion. This rapid and simple model quantitated cocaine abstinence syndrome in a manner that was cocaine-reversible and related to the rate and duration of drug infusion.