Differential mechanism of G-protein activation induced by endogenous mu-opioid peptides, endomorphin and beta-endorphin.

It is well documented that the mu-opioid receptor (MOP-R) is expressed by neurons in several central nervous system regions. Its occupancy with agonist drugs modulate a variety of physiological processes including pain, reward, stress, immune responses, neuroendocrine functions, and cardiovascular control. Based on the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system.

Endomorphin-induced motivational effect: differential mechanism of endomorphin-1 and endomorphin-2.

The newly discovered endogenous mu-opioid receptor (MOP-R) ligands endomorphin-1 (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. This review focuses on differential mechanism of the motivational effects induced by EM-1 and EM-2. In the [35S]GTPgammaS binding assay, either EM-1 or EM-2 causes a concentration-dependent G-protein activation in brain membrane of normal mice, whereas neither EM-1 nor EM-2 produces any activation of G-protein in membranes obtained from the MOP-R knockout mice.

Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.

The role of the histaminergic system in the discriminative stimulus effects of cocaine and methamphetamine was examined in rats trained to discriminate between saline and cocaine (10 mg/kg) or methamphetamine (1.0 mg/kg). L-histidine (400 mg/kg), a precursor of histamine, significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine.

Possible involvement of mu1-opioid receptors in the fentanyl- or morphine-induced antinociception at supraspinal and spinal sites.

Fentanyl has been shown to be a potent analgesic with a lower propensity to produce tolerance and physical dependence in the clinical setting. The present study was designed to investigate the mechanisms of fentanyl- or morphine-induced antinociception at both supraspinal and spinal sites. In the mouse tail-flick test, the antinociceptive effects induced by both fentanyl and morphine were blocked by either the mu1-opioid receptor antagonist naloxonazine or the mu1/mu2-opioid receptor antagonist beta-funaltrexamine (beta-FNA) after s.

Intensification of the development of ethanol dependence in mice lacking dopamine D(3) receptor.

The present study was designed to ascertain the role of dopamine D3 receptors in the development of physical dependence on ethanol using mice lacking the dopamine D3 receptor gene. The mutation eliminated the dopamine D3 receptor without any detectable changes in both dopamine D1 and D2 receptors. The ethanol-induced sleep time in dopamine D3 receptor knockout mice (D3-KO) was longer than that in wild-type mice.

Effect of repeated administration of morphine on the activity of extracellular signal regulated kinase in the mouse brain.

The present study was designed to determine whether chronic morphine treatment could influence the activity of extracellular signal regulated kinase (ERK) in the mouse brain. The single subcutaneous injection of morphine produced profound antinociception and an increase in phosphorylated-ERK (p-ERK) immunoreactivity in the pons/medulla, and these effects were blocked by a mu-opioid receptor antagonist, naloxone. The potency of antinociception induced by the second morphine injection at 24 h after the first morphine injection was similar to that by the first morphine injection.

Regional cerebral blood flow abnormalities in nondemented patients with memory impairment.

Background: Patients with objective evidence of memory impairment have been considered to be at risk for developing Alzheimer's disease (AD). However, little is known about patterns of regional cerebral blood flow abnormalities and their prognostic significance in these patients.

Methods: The authors retrospectively studied 28 nondemented subjects with memory loss and investigated patterns of blood flow abnormalities on single photon emission computed tomography (SPECT).

Effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the discriminative stimulus and rewarding effects of cocaine in rats.

Rationale: We previously demonstrated that the prototypical kappa-opioid receptor agonist U-50,488H did not affect the discriminative stimulus effects of cocaine, and the dose of U-50,488H which significantly induced aversive effects attenuated the rewarding effects of cocaine.

Objectives: In the present study, the effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the discriminative stimulus and rewarding effects of cocaine were examined in rats.

Methods: In the drug discrimination procedure, the effects of TRK-820 on the discriminative stimulus effects of cocaine were examined in rats that had been trained to discriminate between 10 mg/kg cocaine and saline.

Modulation of kappa-opioidergic systems on mecamylamine-precipitated nicotine-withdrawal aversion in rats.

The present study was designed to examine the modulation of the kappa-opioidergic system on mecamylamine-precipitated nicotine-withdrawal aversion. The nicotinic receptor antagonist mecamylamine, which is known to pass the blood-brain barrier, produced a place aversion in rats chronically treated with nicotine using an osmotic mini-pump. This effect was significantly attenuated by pretreatment with -opioid receptor agonists U50,488H (1.

A putative sigma1 receptor antagonist NE-100 attenuates the discriminative stimulus effects of ketamine in rats.

Ketamine, one of the dissociative anaesthetic agents, has been shown to produce psychotomimetic effects. It has been well documented that activation of sigma receptors is responsible for the pathogenesis of some psychiatric disorders. In the present study, the effects of NE-100, a putative sigma(1) receptor antagonist, was investigated in rats trained to discriminate between ketamine (5 mg/kg, i.

Demonstration of bovine herpesvirus type 1 and Mannheimia haemolytica antigens in specimens stored for up to 22 months in buffered formalin.

Bovine herpesvirus type 1 (BHV-1) and Mannheimia haemolytica antigens were demonstrated in lung tissues that were stored in 10% neutral phosphate buffered formalin for 1 to 22 months using the immunoperoxidase method. There were no differences observed in terms of labelling intensity and distribution of M. haemolytica antigens between specimens stored for 1 and 22 months.