title: A tryptamine-derived catecholaminergic enhancer, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], attenuates reinstatement of methamphetamine-seeking behavior in rats.
abstract: Relapse to drug craving is problematic in treatment for drug abuse. Evidence suggests inactivation of dopaminergic neurotransmission during drug withdrawal. Meanwhile, a tryptamine analogue, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], has been reported to enhance electrical stimulation of monoamine release. This study examined the effect of (-)-BPAP on reinstatement of methamphetamine-seeking behavior in an animal model of relapse to drug abuse. Rats were trained to i.v. self-administer methamphetamine paired with a light and tone (methamphetamine-associated cues) under a fixed-ratio 1 schedule of reinforcement for 10 days. After extinction session under saline infusions without cues, a reinstatement test under saline infusions was begun. Reinstatement induced by methamphetamine-associated cues or methamphetamine-priming injections was attenuated by repeated administration of (-)-BPAP during the extinction phase. Acute administration of (-)-BPAP on test day dose-dependently attenuated both reinstatements. Acute administration of (-)-BPAP neither reinstated methamphetamine-seeking behavior alone nor affected methamphetamine self-administration. Pretreatment with either R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH-23390), a dopamine D(1)-like receptor antagonist, or amisulpride, a dopamine D(2)-like receptor antagonist, did not appreciably affected the acute effect of (-)-BPAP on both reinstatements. Co-pretreatment with the dopamine receptor antagonists failed to alter the effects of (-)-BPAP. Meanwhile, pretreatment with a dopamine D(1)-like receptor agonist, (+/-)-6-chloro-7,8-dihydroxy-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297), dose-dependently attenuated reinstatement induced by the cues or methamphetamine-priming injections. In contrast to (-)-BPAP, pretreatment with SCH-23390 reversed the effects of SKF-81297. Our findings suggest activation of dopamine D(1)-like receptors results in attenuation of the reinstatement of methamphetamine-seeking behavior. Additionally, our findings provide evidence to develop (-)-BPAP and dopamine D(1)-like receptor agonists as an anti-relapse medication for methamphetamine abusers.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hiranita
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nawata
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077582:Amisulpride; D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003214:Conditioning, Classical / Q000187:drug effects; D003463:Cues; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C404200:1-(benzofuran-2-yl)-2-propylaminopentane; D018663:Adrenergic Agents; D001552:Benzazepines; D001572:Benzofurans; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C534628:SCH 23390; D008694:Methamphetamine; C067113:SK&F 81297; D013469:Sulpiride; D000077582:Amisulpride