Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 35; no. 11; pp. 2165 - 2178
• Main Authors: MANTSCH, John R, WEYER, Andy, VRANJKOVIC, Oliver, BEYER, Chad E, BAKER, David A, CARETTA, Holly
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.10.2010
• Subjects: Adrenergic Antagonists - pharmacology; Animals; Behavior, Addictive - physiopathology; Behavior, Addictive - psychology; Biological and medical sciences; Cocaine - administration & dosage; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Neuropharmacology; Norepinephrine - physiology; Original; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Adrenergic, beta-2 - physiology; Stress, Psychological - physiopathology; Stress, Psychological - psychology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Imidazole derivatives; Agonist; Relapse; Conditioned place preference; Psychotropic; Quinazoline derivatives; α1-Adrenergic receptor; β-Adrenergic receptor; Imidazoline receptor; Ester; Alpha blocking agent; Noradrenergic transmission; Clonidine; Drug of abuse; Antagonist; Propranolol; α2-Adrenergic receptor; beta adrenergic receptors; CNS stimulant; Rodentia; Catecholamine; Stress; Prazosin; Vertebrata; Mammalia; Mouse; Animal; Neurotransmitter; α-Adrenergic receptor agonist; Cocaine; Norepinephrine; Adrenergic receptor; Beta blocking agent
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2010.86

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- (15 mg/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 (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20-25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/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 β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate.