Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morph...

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...

BACKGROUND AND PURPOSE Hippocampus-dependent memory involves the activity of sharp wave ripples (SWRs), which are thought to participate in the process of memory consolidation. The hippocampus contains high levels of endogenous opioids and of μ-opioid receptors (MORs). Here, we have assessed the role of MOR agonists in the modulation of SWRs. EXPERIMENTAL APPROACH Using recordings of extracel...

Previous in vitro and in vivo studies have determined that the d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity. The present studies examined the ability of d-methadone to attenuate the development of morphine tolerance in mice and rats and to modify NMDA-induced hyperalgesia in rats. A decrease in the percentage of mice analgesic (tail-flick response) after 5 ...

Margas W, Mahmoud S, Ruiz-Velasco V. Muscarinic acetylcholine receptor modulation of Mu ( ) opioid receptors in adult rat sphenopalatine ganglion neurons. J Neurophysiol 103: 172–182, 2010. First published November 4, 2009; doi:10.1152/jn.00295.2009. The sphenopalatine ganglion (SPG) neurons represent the parasympathetic branch of the autonomic nervous system involved in controlling cerebral bl...

Some studies have shown that acetylcholine muscarinic receptors involved in the opiate reward. In the present study, the effect of intra-basolateral amygdale (BLA) acetylcholine muscarinic like receptor agonist (physostigmine) and antagonist (atropine) on the acquisition of morphine-induced place preference has been investigated in male Wistar rats. For this purpose, two 22 gauges guide cannula...

Recent studies have shown that morphine modulates the function of glia cells through both opioid receptor dependent and independent mechanisms. However, the mechanism by which morphine regulates neuronal disorders through the alteration of microglia activity remains unclear. In this study, using rat primary mesencephalic neuron-glia cultures, we report that both l-morphine and its synthetic ste...

BACKGROUND Chronic administration of morphine cause physical dependence but the exact mechanism of this phenomenon remains unclear. The aim of this study is the assessment of systemic and intracerebroventricular (icv) administration of ramelteon (a melatonin receptor agonist) on morphine physical dependence. METHODS 88 adult male rats were divided into 2 major groups, namely "systematic" and ...