Doxycycline diminishes the rewarding and psychomotor effects induced by morphine and cocaine

Amanda J Sales; Pedro H Gobira; João F C Pedrazzi; João R Silveira; Elaine Del Bel; Felipe V Gomes; Francisco S Guimarães

doi:10.1016/j.pnpbp.2023.110870

Doxycycline diminishes the rewarding and psychomotor effects induced by morphine and cocaine

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jan 10:128:110870. doi: 10.1016/j.pnpbp.2023.110870. Epub 2023 Oct 2.

Authors

Amanda J Sales¹, Pedro H Gobira², João F C Pedrazzi³, João R Silveira¹, Elaine Del Bel⁴, Felipe V Gomes¹, Francisco S Guimarães⁵

Affiliations

¹ Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
² Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
³ Departament of Neuroscience, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
⁴ Departament of Phisiology, Faculty of Odontology of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
⁵ Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: fsguimar@fmrp.usp.br.

PMID: 37793480
DOI: 10.1016/j.pnpbp.2023.110870

Abstract

Few pharmacological treatments are available for substance use disorders (SUDs). Neuroplastic changes induced by increased activity of metalloproteinase (MMP) enzymes in the brain are among the several molecular processes that may play a role in drug addiction. Doxycycline, a widely used tetracycline that crosses the blood-brain barrier, inhibits MMPs and has been investigated as a potential treatment for brain disorders. However, the effects of doxycycline on rewarding properties of drugs of abuse remain not investigated. Here, we tested the effects of low doses of doxycycline on the rewarding effects of morphine and cocaine in conditioned place preference (CPP) and locomotor sensitization in mice. Acute doxycycline (10 mg/kg) attenuated the cocaine-induced CPP and hyperlocomotion. Repeated doxycycline (10 mg/kg) blocked hyperlocomotion and attenuated the locomotor sensitization induced by cocaine. It also decreased the rewarding effects in the CPP induced by morphine and cocaine. Our results suggest that doxycycline could be repurposed for treating SUDs.

Keywords: Addiction; Cocaine; Conditioned place preference; Doxycycline; Locomotor sensitization; Morphine.

MeSH terms

Animals
Cocaine* / pharmacology
Doxycycline / pharmacology
Mice
Morphine / pharmacology
Reward
Substance-Related Disorders*

Substances

Morphine
Cocaine
Doxycycline