CRF₁ receptor-deficiency increases cocaine reward

Area of Science:

• Neuroscience
• Pharmacology
• Stress Physiology

Background:

• Stimulant drugs, like cocaine, induce reward and activate stress systems.
• The corticotropin-releasing factor (CRF) and hypothalamus-pituitary-adrenal (HPA) axis are key stress-responsive systems activated by stimulants.
• The precise role of CRF and the HPA axis in stimulant reward is not fully understood.

Purpose of the Study:

• To investigate the role of the CRF1 receptor in cocaine reward.
• To determine if CRF1 receptor function is linked to HPA axis activity in cocaine reward.

Main Methods:

• Utilized CRF1 receptor-deficient (CRF1-/-) mice and wild-type littermates.
• Administered varying doses of cocaine to assess conditioned place preference (CPP).
• Used pharmacological antagonism of the CRF1 receptor with antalarmin.
• Measured plasma corticosterone and brain nuclear glucocorticoid receptor (GR) levels.
• Administered exogenous corticosterone to rescue HPA axis function in CRF1-/- mice.

Main Results:

• CRF1-/- mice exhibited cocaine CPP at a low dose (5 mg/kg), while wild-type mice showed CPP at a high dose (20 mg/kg).
• Pharmacological blockade of CRF1 receptors abolished cocaine reward.
• CRF1-/- mice displayed increased stereotypy responses to cocaine.
• CRF1-/- mice had low corticosterone but elevated hippocampal GR levels.
• Exogenous corticosterone normalized HPA axis function but did not alter CRF1 receptor-dependent cocaine reward, though it increased stereotypy.

Conclusions:

• The CRF1 receptor plays a crucial role in mediating cocaine reward.
• Cocaine reward mediated by the CRF1 receptor is independent of HPA axis activity.
• CRF1 receptor signaling influences behavioral responses to cocaine, including reward and stereotypy.