β-adrenergic receptor mediation of stress-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: roles for β1 and β2 adrenergic receptors

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 342; no. 2; pp. 541 - 551
• Main Authors: Vranjkovic, Oliver, Hang, Shona, Baker, David A, Mantsch, John R
• Format: Journal Article
• Language: English
• Published: United States The American Society for Pharmacology and Experimental Therapeutics 01.08.2012
• Subjects: Adrenergic alpha-2 Receptor Antagonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-1 Receptor Antagonists - pharmacology; Adrenergic beta-2 Receptor Agonists - pharmacology; Adrenergic beta-2 Receptor Antagonists - pharmacology; Adrenergic Neurons - drug effects; Adrenergic Neurons - metabolism; Animals; Behavior, Addictive - chemically induced; Behavior, Addictive - metabolism; Behavior, Addictive - psychology; Clenbuterol - pharmacology; Cocaine - administration & dosage; Cocaine-Related Disorders - etiology; Cocaine-Related Disorders - metabolism; Cocaine-Related Disorders - psychology; Conditioning, Operant - drug effects; Imidazoles - pharmacology; Isoindoles - pharmacology; Isoproterenol - pharmacology; Male; Mice; Motor Activity - drug effects; Neuropharmacology; Receptors, Adrenergic, beta-1 - metabolism; Receptors, Adrenergic, beta-2 - metabolism; Stress, Physiological - physiology; Synaptic Transmission - drug effects
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.112.193615

Stress can trigger the relapse of drug use in recovering cocaine addicts and reinstatement in rodent models through mechanisms that may involve norepinephrine release and β-adrenergic receptor activation. The present study examined the role of β-adrenergic receptor subtypes in the stressor-induced reinstatement of extinguished cocaine-induced (15 mg/kg i.p.) conditioned place preference in mice. Forced swim (6 min at 22°C) stress or activation of central noradrenergic neurotransmission by administration of the selective α(2) adrenergic receptor antagonist 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL-44,408) (10 mg/kg i.p.) induced reinstatement in wild-type, but not β- adrenergic receptor-deficient Adrb1/Adrb2 double-knockout, mice. In contrast, cocaine administration (15 mg/kg i.p.) resulted in reinstatement in both wild-type and β-adrenergic receptor knockout mice. Stress-induced reinstatement probably involved β(2) adrenergic receptors. The β(2) adrenergic receptor antagonist -(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI-118,551) (1 or 2 mg/kg i.p.) blocked reinstatement by forced swim or BRL-44,408, whereas administration of the nonselective β-adrenergic receptor agonist isoproterenol (2 or 4 mg/kg i.p.) or the β(2) adrenergic receptor-selective agonist clenbuterol (2 or 4 mg/kg i.p.) induced reinstatement. Forced swim-induced, but not BRL-44,408-induced, reinstatement was also blocked by a high (20 mg/kg) but not low (10 mg/kg) dose of the β(1) adrenergic receptor antagonist betaxolol, and isoproterenol-induced reinstatement was blocked by pretreatment with either ICI-118,551 or betaxolol, suggesting a potential cooperative role for β(1) and β(2) adrenergic receptors in stress-induced reinstatement. Overall, these findings suggest that targeting β-adrenergic receptors may represent a promising pharmacotherapeutic strategy for preventing drug relapse, particularly in cocaine addicts whose drug use is stress related.