Histological studies were carried out on the degranulation of mesenteric mast cells of white rats caused by injections of morphine and nalorphine hydrochloride intravenously and the following conclusions were obtained. 1. By the injection of morphine hydrochloride fairly significant degranulation of the mesenteric mast cell was observed. 2. In various experimental doses of morphine hydrochloride the cytological change of the degranulation was not proportional to the doses of it in cases given more than 12mg./kg. of body weight. 3. The degranulating effect of the mesenteric mast cell by the injection of morphine hydrochloride was significantly inhibited by an adrenalectomy.
Adrenalectomy ; Animal ; Male ; Mast Cells/drug effects* ; Mesentery/drug effects* ; Morphine/antagonists & inhibitors ; Morphine/pharmacology* ; Nalorphine/pharmacology ; Rats

AIMTo observe the effect and mechanism of scopolamine on morphine(Mor)-induced mice dependence.

METHODSThe Mor-dependent mice model was established by intraperitoneal (ip) administered Mor for seven days. Pain threshold, times of jump and hippocampus intracellular free calcium ion concentration ([Ca2+]i) were determined by the heat plate test, naloxone (Nal)-precipitated jumping response and flow cytometry, respectively.

RESULTSThe pain threshold of Mor-dependent mice decreased significantly while there was a marked increase in times of jump, the rate of jumping animals and hippocampus [Ca2+]i. Co-administered scopolamine, the pain threshold of Mor-dependent mice increased significantly; the number of jump, the rate of jumping animals and hippocampus [Ca2+]i all decreased significantly.

CONCLUSIONScopolamine could antagonize the Mor-induced mice dependence, which could be related to decreasing the levels of brain intracellular free calcium.

Animals ; Calcium ; metabolism ; Hippocampus ; cytology ; drug effects ; metabolism ; Mice ; Mice, Inbred Strains ; Morphine ; pharmacology ; Morphine Dependence ; metabolism ; Scopolamine Hydrobromide ; pharmacology

AIMTo determine whether testosterone is involved in morphine withdrawal syndrome (WS).

METHODSIn order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS.

RESULTSThe severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, i.p.) male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, i.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats.

CONCLUSIONIt can be concluded that testosterone might be effectively involved in morphine WS.

Androgen Antagonists ; pharmacology ; Androgens ; pharmacology ; physiology ; Animals ; Behavior, Animal ; Female ; Flutamide ; pharmacology ; Male ; Morphine ; pharmacology ; Morphine Dependence ; physiopathology ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Narcotics ; pharmacology ; Orchiectomy ; Rats ; Rats, Wistar ; Severity of Illness Index ; Substance Withdrawal Syndrome ; physiopathology ; Testosterone ; pharmacology ; physiology

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

The effects of ginsenosides on the actions of morphine are summarized. It mainly focuses on the antagonistic effects of ginsenosides on morphine-induced changes of animal behaviors, neural system functions and cell signaling transduction.
Animals ; Behavior, Animal ; drug effects ; Body Weight ; drug effects ; Ginsenosides ; pharmacology ; Mice ; Morphine ; antagonists & inhibitors ; pharmacology ; Morphine Dependence ; Neurotransmitter Agents ; metabolism ; Rats ; Signal Transduction ; drug effects

Bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide, is one of the cleavage products of proenkephalin A. It potently activates opioid receptors and sensory neuron-specific receptor (SNSR). The present study was aimed at investigating the effect of BAM22 on morphine tolerance. Intrathecal (i.t.) administration of morphine for 7 d produced morphine tolerance in rats. Then the rats were divided into three groups in which morphine, saline or BAM22 were administered i.t., respectively, on day 8, and morphine was given to all of the animals on day 9. It was found that morphine administered on day 9 resumed antinociceptive effects in BAM22 group, but not in saline or morphine group. The potency of morphine in BAM22 group was 48.5% of the maximal possible effect (MPE) detected by paw withdrawal test and the antinociception persisted for approximately 1 h. Following the similar treatment, morphine administered on day 9 reduced nocifensive behaviors by 3.2 min and 24 min in BAM22 group in the first and second phases, in the formalin test, respectively. The decreases were 45% and 82% of the corresponding values observed in saline group. Furthermore, following the treatment with BAM22 (10 nmol) on day 8 in morphine-tolerance rats, morphine administered on day 9 decreased the expressions of the heat-evoked c-Fos-like immunoreactivity (FLI) protein by approximately 80% in laminae I-II, III-IV and V-VI in the spinal cord at L4-L5 compared with that in saline or morphine group. The present study provided evidence at behavioral and cellular levels showing that BAM22 resumed antinociception of morphine. The results that the reversal effect of BAM22 on morphine tolerance was more efficient in persistent pain model than in acute pain may indicate that BAM22 differentially modulates morphine tolerance. The present study suggests that SNSR is involved in the modulation of morphine tolerance.
Animals ; Drug Tolerance ; Enkephalins ; pharmacology ; Morphine ; pharmacology ; Pain ; drug therapy ; Peptide Fragments ; pharmacology ; Rats ; Receptors, G-Protein-Coupled ; metabolism

AIMTo investigate the effect of morphine on fetal movement, heart rate, hatch weight, hatch days and hatch rate.

METHODSMorphine was injected into airspace of eggs and fetal movement, heart rate, hatch weight, hatch days and hatch rates were recorded.

RESULTSHatch days were shorter, hatch rates were lower and some chicks became motor disorder for morphine. Chicks with morphine exposure 20 mg/kg from E 12 to E 16 had highest hatch rate and lowest disable rate. Morphine reduced fetal movement, increased heart rate (P < 0.05).

CONCLUSIONThe development of chick embryo is impaired by morphine exposure and the magnitude of these effects depends on the drug dose and the length of time that the developing organism is exposed to morphine.

Animals ; Chick Embryo ; drug effects ; growth & development ; Chickens ; growth & development ; Morphine ; pharmacology

Acupuncture Therapy ; Analgesia ; Animals ; Brain Chemistry ; Morphine ; pharmacology ; Opium ; analogs & derivatives ; antagonists & inhibitors ; Rats

OBJECTIVETo investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior.

METHODSSD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system.

RESULTSIn rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period.

CONCLUSIONMorphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.

Animals ; Cerebral Cortex ; drug effects ; physiology ; Drug-Seeking Behavior ; physiology ; Electrophysiological Phenomena ; Extinction, Psychological ; Morphine ; pharmacology ; Morphine Dependence ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Telemetry

Drug addiction is considered as a chronic, recurrent brain disease characterized by relapse. Repeated exposure to certain drugs, such as morphine, can produce deleterious sequelae, such as drug dependence, tolerance and compulsive drug seeking. In the present study, we investigated the dependence and psychological craving for morphine in rats using the conditioned place preference (CPP) paradigm. On the other hand, to study the effect of morphine on hippocampal sensory gating (N40), double click auditory-evoked potential was recorded during the chronic morphine administration, withdrawal and re-exposure to morphine in rats. The rats in morphine group received a course of morphine (10 mg/kg, i.p.) injection for 12 d, followed by 12 d of withdrawal, 1 d of re-exposure to morphine (2.5 mg/kg, i.p.) and 2 d of the second withdrawal. The rats in the control group were treated in the same way except that saline was applied instead of morphine. CPP test demonstrated that the method of drug administration in the present study induced dependence and psychological craving for morphine in rats. The results in the double click auditory-evoked potential experiment showed that during the chronic morphine administration, hippocampal N40 gating was damaged. In the initial 2 d of the first withdrawal hippocampal N40 gating in morphine group was reduced compared with that in the control group and it was significantly greater on the 3rd day, and then recovered gradually to the normal level from day 4 to day 12. After re-exposure to morphine, hippocampal N40 gating in morphine group was significantly reduced compared with that in the control group, and it remained at a lower level during the following 2 d, suggesting that hippocampal N40 gating in rats was more sensitive to morphine during re-exposure. Our results suggest that long-term repeated morphine administration and re-exposure to morphine disrupt hippocampal N40 gating, and that the effect of morphine addiction on the brain is possibly long-term.
Animals ; Conditioning (Psychology) ; drug effects ; Evoked Potentials, Auditory ; drug effects ; Hippocampus ; physiopathology ; Male ; Morphine ; pharmacology ; Morphine Dependence ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome ; physiopathology