10 research outputs found
Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for ÎČ-2 Adrenergic Receptors
The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15âmg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15âmg/kg), exposure to a stressor (6-min forced swim (FS); 20â25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2âmg/kg, i.p.) or BRL44408 (5, 10âmg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective ÎČ-AR antagonist, propranolol (5, 10âmg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2âmg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3âmg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03âmg/kg) but not high (0.3âmg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of ÎČ-ARs. The ÎČ-2 AR antagonist ICI-118551 (1âmg/kg, i.p.), but not the ÎČ-1 AR antagonist betaxolol (10âmg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through ÎČ-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate