Morphine administered simultaneously to intracerebroventricular (i.c.v.) and intrathecal (i.t.) sites exhibits synergism, with the antinociceptive potency much greater than would be predicted from a simple addition of the potencies of the same dose administered to either site alone. This synergism was quantified in mice using both a fixed dose method, in which the morphine dose at one site was ...

BACKGROUND Glycogen-synthase kinase 3 (GSK3) is involved in many signaling pathways and is associated with a host of high-profile pathophysiological states. However, its role in morphine tolerance, especially naloxone-precipitated withdrawal syndrome, has not been well investigated. The present study was undertaken to study the role of GSK3 in chronic morphine exposure. METHODS Adult male Spr...

1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brain synaptosomes was also investigated. 2. Pretreatment with Org 6582, citalopra...

We report an anatomically defined opioid-responsive site in the rostral agranular insular cortex (RAIC) of the rat and characterize the antinociception produced by morphine acting within this region. Immunohistochemistry for the mu-opioid receptor identified a discretely localized cluster of densely labeled dendrite-like processes in the agranular insular cortex. The antinociceptive effect of m...

In the present study the effects of both CCK receptor agonists and antagonists on antinociception induced by morphine in the tail-flick test have been evaluated. M orphine induced dose-dependent antinociception in mice. The response of morphine was potentiated by sulfated cholecystokinin-8 (CCK-8S) but not by unsulfated cholecystokinin-8 (CCK-8U). The CCK receptor antagonists MK-329 and L-...

The functional interactions between supraspinal p, and 8 receptors were characterized in the mouse using p, receptor-selective antagonists. The effects of pretreatment with the p, opioid antagonists, /~-funaltrexamine (/'/-FNA) and naloxonazine on the modulation of morphine antinociception by the 8 agonists [D-PenZ,D-PenS]enkephalin (DPI)PE) and [D-AlaZ,MetS]enkephalinamide (DAMA) were studied....

in the present study, the effect of gaba (γ-aminobutyric acid) receptor agonists and antagonists on morphine-induced antinociception was investigated in formalin test in rats. intraperitoneal (i.p.) injection of different doses of morphine (1, 3, 6 and 9 mg/kg) and intracerebroventricular (i.c.v.) injection of different doses of muscimol (0.5, 1 and 2 g/rat) or baclofen (0.25, 0.5 and 1 g/rat) ...

Morphine induces peripherally μ-opioid-mediated antinociception to heat but not to mechanical stimulation. Peripheral sigma-1 receptors tonically inhibit μ-opioid antinociception to mechanical stimuli, but it is unknown whether they modulate μ-opioid heat antinociception. We hypothesized that sigma-1 receptors might play a role in the modality-specific peripheral antinociceptive effects of morp...

The effect of pretreatment with naloxonazine on opioid-mediated antinociception against a thermal stimulus (55 degrees C warm-water tail-flick test) and inhibition of gastrointestinal transit at supraspinal and spinal levels was studied in unanesthetized mice. The mu-selective agonist [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the delta-selective agonist [D-Pen2, D-Pen5]enkephalin (DPDP...