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

Cues associated with dangerous or rewarding outcomes can themselves elicit neural activation. 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 in discrete brain regions. Activation of the prefrontal cortex has been shown to be particularly prominent. Some studies have also shown prefrontal cortical activation following exposure to fear-inducing stimuli. To investigate the specificity of regional brain Fos activation, we treated rats with an anxiogenic drug, yohimbine (2 mg/kg, intraperitoneally (i.p.)), or water once per day for 10 consecutive days in a test environment 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 environment where they had previously been treated with yohimbine showed conditioned increases in motor activity compared with controls. Fos expression was increased in several brain regions, including the basolateral amygdala, but was unchanged in prefrontal cortex, in contrast to what has been reported for rewarding drugs. These observations show a neural activation profile elicited by cues associated with the anxiogenic drug yohimbine and further support the hypothesis that prefrontal cortex has a specific role in reward expectancy.