The regulation of glutamate (Glu) release from the excitatory input to dopamine cells in the ventral tegmental area (VTA) during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. EPSCs were inhibited by opioid agonists acting at micro-subtype receptors but not by selective delta- or kappa-subtype agonists. The opioid inhibition was reduced by 65%...

The present study was designed to examine sex differences in complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia and sex differences in opioid antinociception and anti-hyperalgesia. Female rats developed inflammation and hyperalgesia faster and exhibited greater peak hyperalgesia than male rats. In arthritic (CFA-treated) rats, lower thresholds were observed during estrus and proes...

As a follow-up study to an earlier report that racemic fenfluramine can acutely potentiate the analgesic effects of morphine in humans, we investigated the effects of fenfluramine on the development of tolerance to morphine analgesia in rats. Antinociceptive effect, as measured by the tail-flick latency, was studied over 8 days in rats that received continuous i.v. infusion of 1) 22 mg/kg/day o...

AIMS The current study assessed the in vivo antagonist properties of nalmefene using procedures previously used to characterize the opioid antagonists naloxone, naltrexone, 6beta-naltrexol and nalbuphine. MAIN METHODS ICR mice were used to generate antagonist dose-response curves with intraperitoneal (i.p.) nalmefene against fixed A(90) doses of morphine in models of morphine-stimulated hyper...

DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) and [Dmt ]DALDA (H-DmtD-Arg-Phe-Lys-NH2) (Dmt 5 29,69-dimethyltyrosine) are potent and highly selective m-opioid agonists (Ki d/Ki m . 10,000 and Ki k/Ki m . 100). Both peptides carry a 31 charge at physiological pH. Their antinociceptive and respiratory effects were compared with morphine (MOR) after intrathecal administration in rats. Both DALDA and [Dmt]DALDA ...

Nitazenes are a group of compounds developed in the 1950s as opioid analgesics, but they were never approved to market. As such, not well known outside academic research laboratories. A characteristic nitazenes is their high potency (e.g., hundreds thousands fold more potent than morphine and other opioids tenfold fentanyl). In past few years, several nitazenes, including “designer analogs,” ha...

BACKGROUND Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mu...

Ultra-low doses of non-selective α2-adrenoceptor antagonists augment acute spinal morphine antinociception and block morphine tolerance; however, the receptor involved in mediating these effects is currently unknown. Here, we used tail flick and paw pressure tests on the rat to investigate the acute analgesic and tolerance-inducing effects of spinal morphine and norepinephrine alone or in combi...

Opioids are used in humans in the management of chronic osteoarticular pains, but the development of tolerance to the analgesic effects after continuous administration is still not well understood. Our aim was to characterize morphine tolerance in a murine model of arthritis that mimics the sequence of events occurring in humans. Inflammation was induced by the intraplantar injection of complet...

Chronic opioid antagonist treatment up-regulates opioid receptors and produces functional supersensitivity. Although opioid antagonists vary from neutral to inverse, the role of antagonist efficacy in mediating the chronic effects of opioid antagonists is not known. In this study, the effects of two putative inverse agonists (naltrexone, naloxone) and a putative neutral antagonist (6 -naltrexol...