The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse.
BACKGROUND
Brain noradrenaline is involved in footshock stress-induced reinstatement of drug seeking in a rat relapse model. We studied whether yohimbine, an alpha-2 adrenoceptor antagonist that increases noradrenaline release and induces anxiety-like responses in human and nonhuman subjects, would reinstate methamphetamine seeking in rats.


METHODS
In experiment 1, the effect of yohimbine (1.25-2.5 mg/kg) on reinstatement was compared with that of intermittent footshock (5 min;.2-.6 mA) in rats that were trained to lever press for intravenous methamphetamine (9-11 days) and subsequently underwent 7 days of extinction training. In experiment 2, the effect of yohimbine on reinstatement of drug seeking was determined during early (1 day) and late (21 or 51 days) withdrawal periods. On the test days, rats were first given 3-hour extinction sessions and were then tested for reinstatement induced by yohimbine.


RESULTS
In experiment 1, both yohimbine and footshock stress reinstated methamphetamine seeking after extinction. In experiment 2, extinction responding was higher after 21 or 51 withdrawal days than after 1 withdrawal day. In contrast, no significant time-dependent changes in yohimbine-induced reinstatement were observed.


CONCLUSIONS
Results indicate that yohimbine is a potent stimulus for reinstatement of methamphetamine seeking in a rat relapse model.
Shepard
Jack D
JD
Cellular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224, USA.
Bossert
Jennifer M
JM
Liu
Shirley Y
SY
Shaham
Yavin
Y
D000317:Adrenergic alpha-Antagonists / Q000633:toxicity; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004597:Electroshock / Q000379:methods; D005108:Extinction, Psychological / Q000502:physiology; D008297:Male; D008694:Methamphetamine; D023421:Models, Animal; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D019966:Substance-Related Disorders / Q000209:etiology* / Q000523:psychology; D013997:Time Factors; D015016:Yohimbine / Q000633:toxicity*
D000317:Adrenergic alpha-Antagonists; D015016:Yohimbine; D008694:Methamphetamine