Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Opioid use disorder (OUD) presents significant public health challenges, marked by high relapse rates and poor treatment retention.
• Oxycodone self-administration and conditioned cue reactivity are key factors contributing to OUD relapse.
• Serotonin 5-HT_2C receptor (5-HT_2CR) neurotransmission influences psychostimulant reward and cue reactivity.

Purpose of the Study:

• To investigate the potential of lorcaserin, a selective 5-HT_2CR agonist, to suppress oxycodone self-administration.
• To evaluate lorcaserin's efficacy in reducing oxycodone-associated cue reactivity in a rat model.
• To explore the therapeutic potential of lorcaserin for treating OUD.

Main Methods:

• Rats were trained to self-administer oxycodone.
• The effects of lorcaserin (0.25-1 mg/kg) on oxycodone intake and cue reactivity were assessed.
• Selective 5-HT_2CR antagonist SB242084 was used to block lorcaserin's effects.
• Cue reactivity was measured using discrete cue complexes in abstinence and extinction-reinstatement models.

Main Results:

• Lorcaserin significantly inhibited oxycodone self-administration.
• This inhibitory effect was reversed by the selective 5-HT_2CR antagonist SB242084.
• Lorcaserin decreased responding to cues previously associated with oxycodone delivery.
• The tested doses of lorcaserin did not affect spontaneous behaviors or operant responding on inactive levers.

Conclusions:

• Lorcaserin demonstrates efficacy in reducing both oxycodone self-administration and cue-induced relapse behaviors.
• The findings highlight the role of the 5-HT_2CR in mediating the effects of oxycodone.
• Lorcaserin shows therapeutic promise for the treatment of opioid use disorder.