The analgesia produced by inhibitory G protein-coupled receptor agonists involves coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying potassium channels (GIRKs) and presynaptic inhibition of neurotransmitter release through regulation of voltage-gated Ca(2+) channels. Here, we used mice lacking the GIRK2 channel subunit to assess the relative contribution of these two ...

There has been no previous demonstration of opioid tolerance and dependence with respect to the propulsive and contractile activities of the gut in vivo. In the experiments described herein, morphine was administered continuously (1 mg/kg/hr s.c., 72 hr) and/or by bolus injection (2 mg/kg) and intestinal motility and transit were evaluated in unanesthetized rats. Tolerance in intestinal motilit...

This study investigated the role of K(ATP) channels in morphine-induced antinociception and hepatic oxidative stress in acute and inflammatory pain. The K(ATP) channel modulators (K(ATP) channel opener, diazoxide 100 mg/kg, p.o, and K(ATP) channel blocker, glibenclamide, 3 mg/kg i.p.) were administered with morphine (80 mg/kg, i.p.). Antinociception was assessed by the tail-flick and formalin t...

The effect of majonoside-R2 on morphine- and U-50,488H-induced antinociception was examined by the tail-pinch test in mice and compared with that of diazepam. Majonoside-R2 and diazepam inhibited the morphine- and U-50,488H-induced antinociception, and the actions were antagonized by the benzodiazepine receptor antagonist flumazenil and the GABA-gated CI- channel blocker picrotoxin. Diazepam bu...

UNLABELLED Antinociception can be produced at the spinal level by activation of opioidergic, noradrenergic, and serotonergic systems. We tested the antinociceptive effects of combined activation of all three systems. Antinociception was assessed in the rat tail-flick test, and drugs were administered via an intrathecal catheter. Morphine, the norepinephrine uptake inhibitor desipramine, and ser...

Regulator of G-protein signaling (RGS) proteins classically function as negative modulators of G-protein-coupled receptor signaling. In vitro, RGS proteins have been shown to inhibit signaling by agonists at the μ-opioid receptor, including morphine. The goal of the present study was to evaluate the contribution of endogenous RGS proteins to the antinociceptive effects of morphine and other opi...

Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate), (visceral, acetic acid), and (...

Paradoxical sleep deprivation (PSD) increases pain sensitivity and reduces morphine antinociception. Because dopaminergic neurons in the periaqueductal gray matter (PAG) participate in pain modulation and opioid-induced antinociception, we evaluated the effects of PSD on thermal pain sensitivity, morphine- and L-DOPA-induced antinociception and dopaminergic functionality in the PAG by assessing...