Semaglutide suppresses cocaine taking, seeking, and cocaine-evoked dopamine levels in the nucleus accumbens

Jul 11, 2025European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Semaglutide reduces cocaine use, craving, and dopamine release in the brain's reward area

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Semaglutide decreased cocaine self-administration and motivation to consume cocaine in male rats.

Cocaine use disorder is linked with intense cravings and compulsive behavior, but no current pharmaceutical treatments exist.
Semaglutide, a long-acting GLP-1 receptor agonist, shows potential benefits due to its greater potency compared to shorter-acting alternatives.
In male rats, semaglutide reduced voluntary cocaine consumption and the motivation to seek cocaine.
The drug also decreased the reinstatement of cocaine-seeking behavior after a period of abstinence.
Semaglutide lowered cocaine-induced dopamine levels in the nucleus accumbens of both mice and rats.
The tested doses of semaglutide did not affect kaolin intake, suggesting no aversive side effects in cocaine-experienced rats.

AI simplified

Currently, no pharmaceutical treatments exist for cocaine use disorder, which is characterized by dysregulated motivation, intense drug craving, compulsive drug-seeking behavior, and relapse during abstinence. While short-acting glucagon-like peptide-1 receptor (GLP-1R) reduces cocaine-related behaviors, its impact is limited by low affinity towards GLP-1R. Semaglutide may be beneficial in this context as it is long-acting with greater potency and affinity for the GLP-1R. Its superiority is substantiated in studies on alcohol and alcohol use disorder (AUD) as it profoundly reduces alcohol intake in animals and patients with AUD, whereas exendin-4 (Ex4) slightly reduces alcohol intake in rats, whereas it does not alter alcohol intake in AUD patients. However, it remains to be explored whether its beneficial effects extend to more complex cocaine-related behaviors, the aim of the present study. Using the cocaine self-administration paradigm in male rats, we tested the efficacy of different doses of semaglutide to reduce voluntary cocaine taking, the motivation to consume cocaine, and the reinstatement of cocaine-seeking behavior. Furthermore, we explored the effects of semaglutide on cocaine-evoked dopamine levels in the nucleus accumbens (NAc). Semaglutide decreased cocaine self-administration, the motivation to consume cocaine, and cocaine reinstatement in male rats. Moreover, semaglutide attenuated cocaine-induced elevation of dopamine levels in mice and rats. Additionally, neither of the tested doses altered kaolin intake, a measurement of malaise, in cocaine-experienced rats. These findings further support the role of GLP-1R in cocaine taking and imply that semaglutide should be tested as a candidate for treating cocaine use disorder.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Semaglutide suppresses cocaine taking, seeking, and cocaine-evoked dopamine levels in the nucleus accumbens

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief