A tryptamine-derived catecholaminergic enhancer, (−)-1-(benzofuran-2-yl)-2-propylaminopentane [(−)-BPAP], attenuates reinstatement of methamphetamine-seeking behavior in rats

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 D1-like receptor antagonist, or amisulpride, a dopamine D2-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 D1-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 D1-like receptors results in attenuation of the reinstatement of methamphetamine-seeking behavior. Additionally, our findings provide evidence to develop (−)-BPAP and dopamine D1-like receptor agonists as an anti-relapse medication for methamphetamine abusers.