Increased anxiety-like behavior of rats during amphetamine withdrawal is reversed by CRF2 receptor antagonism

Withdrawal from psychostimulants increases anxiety states, and amphetamine-treated rats show increased CRF2 receptors in the serotonergic cell body region, the dorsal raphe nucleus (dRN). In the current study, amphetamine (2.5 mg/kg, i.p., 14 days) pre-treated rats spent less time in open arms of the elevated plus maze compared saline pre-treated rats at both 24 h or 2 weeks of withdrawal, and CRF2 receptor antagonism (ASV-30; 2 μg/0.5 μl) within the dRN reversed the effects of amphetamine withdrawal on anxiety-like behavior. Overall, results suggest that CRF2 receptor antagonism may be a novel pharmacological target for anxiety states during drug withdrawal.