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

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.