The Effects of the Dopamine Transporter Ligands JJC8-088 and JJC8-091 on Cocaine versus Food Choice in Rhesus Monkeys.

Although there are no Food and Drug Administration-approved treatments for cocaine use disorder, several modafinil analogs have demonstrated promise in reducing cocaine self-administration and reinstatement in rats. Furthermore, the range of dopamine transporter (DAT) compounds provides an opportunity to develop pharmacotherapeutics without abuse liability. This study extended the comparison of JJC8-088 and JJC8-091, the former compound having higher DAT affinity and predicted abuse liability, to rhesus monkeys using a concurrent cocaine versus food schedule of reinforcement.

Quality and safety in the literature: October 2022.

Healthcare quality and safety span multiple topics across the spectrum of academic and clinical disciplines. Keeping abreast of the rapidly growing body of work can be challenging. In this series, we provide succinct summaries of selected relevant studies published in the last several months.

Chronic phenmetrazine treatment promotes D dopaminergic and α2-adrenergic receptor desensitization and alters phosphorylation of signaling proteins and local cerebral glucose metabolism in the rat brain.

Phenmetrazine (PHEN) is a putative treatment for cocaine and psychostimulant recidivism; however, neurochemical changes underlying its activity have not been fully elucidated. We sought to characterize brain homeostatic adaptations to chronic PHEN, specifically on functional brain activity (local cerebral glucose utilization), G-Protein Coupled Receptor-stimulated G-protein activation, and phosphorylation of ERK1/2, GSK3β, and DARPP-32. Male Sprague-Dawley rats were implanted with sub-cutaneous minipumps delivering either saline (vehicle), acute (2-day) or chronic (14-day) low dose (25 mg/kg/day) or high dose (50 mg/kg/day) PHEN.

Metabotropic glutamate 2,3 receptor stimulation desensitizes agonist activation of G-protein signaling and alters transcription regulators in mesocorticolimbic brain regions.

Metabotropic glutamate (mGlu) receptors are regulators of glutamate release and targets for development of therapies for hyperactive glutamatergic signaling. However, the effects of long-term stimulation of mGlu receptors on cellular signaling in the brain have not been described. This study investigated the effects of 2-day and 14-day osmotic mini-pump administration of the mGlu2,3 agonist LY379268 (3.

Emerging Insights into Mu Opioid Pharmacology.

Opioid analgesics, most of which act through mu opioid receptors, have long represented valuable therapeutic agents to treat severe pain. Concerted drug development efforts for over a 100 years have resulted in a large variety of opioid analgesics used in the clinic, but all of them continue to exhibit the side effects, especially respiratory depression, that have long plagued the use of morphine. The recent explosion in fatalities resulting from overdose of prescription and synthetic opioids has dramatically increased the need for safer analgesics, but recent developments in mu receptor research have provided new strategies to develop such drugs.