CRF2 Receptor Agonists and Nicotine Withdrawal

Corticotropin-releasing factor (CRF) and the urocortins (Ucn1, Ucn2, and Ucn3) belong to the mammalian CRF family of peptides, having similar amino acidic structures but different pharmacological profiles. Their actions are mediated by two distinct receptors, CRF1 and CRF2. CRF and Ucn1 bind to both CRF receptors, whereas Ucn2 and Ucn3 bind selectively to CRF2. Several studies reported that the administration of selective CRF1 antagonists prevents the dysphoria and the reward deficit observed during nicotine withdrawal. Another study referred that the administration of nonselective CRF2 agonists, such as CRF and Ucn1, prevents the hyperphagia and the weight gain assessed during nicotine withdrawal. However, our study was the first to demonstrate that intracerebroventricular administration of Ucn2 and Ucn3 ameliorates the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal, suggesting that the selective CRF2 agonists can be potential candidates in the therapy of nicotine withdrawal.