title: β-adrenergic receptor mediation of stress-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: roles for β1 and β2 adrenergic receptors.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53201, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vranjkovic
authors.forename: Shona
authors.initials: S
authors.lastname: Hang
authors.forename: David A
authors.initials: DA
authors.lastname: Baker
authors.forename: John R
authors.initials: JR
authors.lastname: Mantsch
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology; D002976:Clenbuterol / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D007093:Imidazoles; D054833:Isoindoles; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D003042:Cocaine; D007545:Isoproterenol; D002976:Clenbuterol; C072125:BRL 44408