Neural activation profile elicited by cues associated with the anxiogenic drug yohimbine differs from that observed forreward-paired cues

Abstract

Cues associated with dangerous or rewarding outcomes can themselves elicit neuralactivation. Previous work in rats has shown that cues associated with morphine, cocaine, nicotine or palatable food can elicit enhanced expression of the immediate-early gene product Fos indiscrete brain regions. Activation of the prefrontalcortex has been shown to be particularly prominent. Some studies have also shownprefrontalcorticalactivation following exposure to fear-inducing stimuli. To investigate the specificity of regionalbrainFos activation, wetreated rats with an anxiogenic drug, yohimbine (2 mg/kg, intraperitoneally (i.p.)), or water once per day for 10 consecutive days in a testenvironment distinct from their home cages. Yohimbine elicited a robust locomotor response that progressively sensitized over days.After a 4-day interval, rats were reintroduced to the paired environment, without drug treatment. Rats re-exposed to the environmentwhere they had previously been treated with yohimbine showed conditioned increases in motor activity compared with controls. Fosexpression was increased in severalbrain regions, includingthebasolateralamygdala, but was unchanged in prefrontalcortex, in contrastto what has been reported for rewarding drugs. These observations show a neuralactivation profile elicited by cues associated with theanxiogenic drug yohimbine and further support the hypothesis that prefrontalcortex has a specific role in reward expectancy. © 2003 American College of Neuropsychopharmacology.