yqa14 and Morphine-Dependence

Increasing preclinical evidence demonstrates that dopamine D3 receptor (D3R) antagonists are a potential option for the treatment of drug addiction. The reinstatement of the addiction can be triggered by environmental stimuli that acquire motivational salience through repeated associations with the drug's effects. YQA14 is a novel D3R antagonist that has exhibited pharmacotherapeutic efficacy in reducing cocaine and amphetamine reward and relapse to drug seeking in mice. In this study we investigated the effects of YQA14 on morphine-induced context-specific locomotor sensitization in mice. We showed that repeated injection of YQA14 (6.25-25 mg/kg every day ip) prior to morphine (10 mg/kg every day sc) not only inhibited the acquisition, but also significantly attenuated the expression of morphine-induced locomotor sensitization. Furthermore, in the expression phase, one single injection of YQA14 (6.25-25 mg/kg, ip) dose-dependently inhibited the expression of morphine-induced behavioral sensitization. Moreover, YQA14 inhibited the expression of morphine-induced behavioral sensitization in wild mice (WT), but not in D3R knockout (D3R

Topics: Animals; Benzoxazoles; Dopamine Antagonists; Drug-Seeking Behavior; Injections, Intraperitoneal; Male; Mice, Knockout; Morphine; Morphine Dependence; Motor Activity; Piperazines; Receptors, Dopamine D3

Increasing evidence suggests that the mesolimbic dopamine system plays a critical role in opioid addiction. However, there is currently no standard drug treatment for opioid addiction. Growing preclinical evidence indicates that the dopamine D(3) receptor antagonists are the potential anti-addiction pharmacotherapeutic agents based on animal models of multiple drug addiction. In this study, we investigated the inhibitory effects of YQA14, a novel dopamine D(3) receptor antagonist with a high affinity and selectivity for dopamine D(3) receptor, using morphine-induced conditioned place preference (CPP) in rats. The results suggested that YQA14 (6.25-25 mg/kg; intraperitoneal, i.p.) decreased the expression of morphine (10 mg/kg, s.c.)-induced CPP in a dose-related manner but did not influence the acquisition of morphine-induced CPP. At a 25 mg/kg dose of YQA14, it also notably inhibited the reactivation of morphine-priming CPP. These findings suggest that YQA14 is a potential agent for anti-opioid addiction which warrants further study and development.

Topics: Animals; Behavior, Animal; Benzoxazoles; Conditioning, Psychological; Dopamine Antagonists; Extinction, Psychological; Male; Morphine Dependence; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D3