BACKGROUND Activation of the cyclic adenosine monophosphate (cAMP)/phosphorylated CREB (P-CREB) system in different brain regions has been implicated in mediating opioid tolerance and dependence, while alteration of this system in the lateral hypothalamus (LH) has been suggested to have a role in food intake and body weight. METHODS Given that opioids regulate food intake, we measured P-CREB ...

Previous experiments have shown that mice lacking a functional delta-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine. Here we report that mice lacking a functional gene for the endogenous ligand preproenkephalin (ppENK) show a similar tolerance deficit. In addition, we found that the DOR-1 and ppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse...

Previous reports utilizing pharmacological antagonists implicate kainate receptor (KAR) activation in the development of morphine tolerance, dependence, conditioned place preference (CPP), and locomotor sensitization, but the role of glutamate receptor (GluR) 5-containing KAR in these effects remains unclear because of limited selectivity of the inhibitors employed. Therefore, we examined respo...

The kappa receptor-selective agonist U-50, 488 was administered chronically to rhesus monkeys. Tolerance developed to the overt behavioral effects of U-50,488 without cross-tolerance to morphine. Withdrawal behaviors produced by deprivation, naloxone or quadazocine administration in U-50, 488-dependent monkeys consisted of hyperactivity, excessive grooming, and yawning. The syndrome was suppres...

Effect of Otostegia persica on naloxone-induced morphine withdrawal syndrome was studied in male mice. Dependence was induced using daily subcutaneous injections of morphine for three days. Morphine was injected to mice at doses of 30 and 45mg/kg on day 1 and 60 and 90mg/kg on day 2 (8:00 am and 6:00 pm). On day 3, morphine (90mg/kg) was injected 1h before oral administration and 1.5h before in...

In the present study, interactive effects of D1 and D2 dopamine receptors antagonists and different periods of lithium pretreatment on morphine dependence in mice have been investigated. This study was designed to investigate whether the hypothesis that lithium and dopaminergic mechanisms via their effects on phosphoinositide pathways and calcium flux could influence morphine withdrawal respons...

Regulators of G protein signaling (RGS) are a family of proteins known to accelerate termination of effector stimulation after G protein receptor activation. RGS9-2, a brain-specific splice variant of the RGS9 gene, is highly enriched in striatum and also expressed at much lower levels in periaqueductal gray and spinal cord, structures known to mediate various actions of morphine and other opia...

The glycine site (MRZ 2/570 and L-701,324), and uncompetitive (MRZ 2/579) NMDA receptor antagonists inhibited morphine-produced behaviors related to drug-abuse. The expression of morphine dependence was blocked by pretreatment with all three compounds (3–7.5 mg/kg); the effects of glycine/NMDA antagonists were not dose-dependent. Mice which were morphine-free for 3 days still displayed a signif...

Morphine dependence is associated with long-term adaptive changes in the brain that involve gene expression. Different behavioral effects of morphine are mediated by different brain regions, for example, the locus ceruleus (LC), a noradrenergic nucleus, is implicated in physical dependence and withdrawal, whereas the ventral tegmental area (VTA), a dopaminergic nucleus, contributes to rewarding...

Background: There is growing evidence indicating that neuronal calcium channels play an important role in the mechanism of Morphine dependence. Objective: To investigate the acute and long-term effects of Verapamil in Morphine dependent mice. Methods: Mice were rendered dependent on Morphine by subcutaneous injection of Morphine over a period of 5 days. The effects of acute and chronic administ...