Objective: To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms. METHODS: Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP. RESULTS: Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA. CONCLUSIONS MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.
Animals ; Ejaculation ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology* ; Female ; Male ; Paraventricular Hypothalamic Nucleus/physiology* ; Peptide Fragments/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu/physiology* ; Somatostatin/pharmacology* ; Sympathetic Nervous System/physiology*

Learning/memory impairment is one of the most serious problems induced by stress, and the underlying mechanisms remain unclear. Opiates and opioid receptors are implicated in multiple physiological functions including learning and memory. However, there is no clear evidence whether the endogenous opioid system is involved in the formation of the stress-induced spatial reference memory impairment. The aim of the present study was to evaluate the role of μ opioid receptor in the stress-induced spatial reference memory impairment by means of Morris water maze (MWM) test in a mouse elevated platform stress model. The mice were trained in the MWM for four trials a session for 4 consecutive days after receiving the elevated platform stress, and intracerebroventricular injection of μ opioid receptor agonist DAMGO, antagonist CTAP or saline. Retention of the spatial training was assessed 24 h after the last training session with a 60-s free-swim probe trial using a new starting position. The results showed that intracerebroventricular injection of μ opioid receptor agonist DAMGO but not antagonist CTAP before MWM training impaired the memory retrieval of mice. Elevated platform stress before MWM training also impaired memory retrieval, which could be reversed by pre-injection of CTAP, and aggravated by DAMGO. These results suggest that endogenous opioid system may play a crucial role in the formation of the stress-induced memory impairment.
Animals ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; pharmacology ; Maze Learning ; Memory Disorders ; Mice ; Receptors, Opioid, mu ; physiology ; Spatial Memory ; Stress, Physiological

OBJECTIVETo investigate the effect of µ-opioid receptors (µ-ORs) in the central nucleus of the amygdala (CeA) on feeding and drinking behaviors in rats and evaluate the role of glutamate signaling in opioid-mediated ingestive behaviors.

METHODSStainless steel cannulas were implanted in the unilateral CeA for microinjection of different doses of the selective µ-OR agonist DAMGO in satiated or water-deprived male SD rats. The subsequent food intake or water intake of the rats was measured at 60, 120, and 240 min after the injection. The rats receiving microinjections of naloxone (NTX, a nonselective opioid antagonist) or D-AP-5 (a selective N-methyl-D-aspartic acid-type glutamate receptor antagonist) prior to DAMGO microinjection were tested for food intake at 60, 120, and 240 min after the injections.

RESULTSInjections of DAMGO (1-4 nmol in 0.5 µl) into the CeA significantly increased food intake in satiated rats, but did not affect water intake in rats with water deprivation. NTX (26.5 nmol in 0.5 µl) injected into the CeA antagonized DAMGO-induced feeding but D-AP-5 (6.3-25.4 nmol in 0.5 µl) injections did not produce such an effect.

CONCLUSIONµ-ORs in the CeA regulate food intake rather than water intake in rats, and the orexigenic role of µ-ORs is not dependent on the activation of the NMDA receptors in the CeA.

2-Amino-5-phosphonovalerate ; pharmacology ; Animals ; Central Amygdaloid Nucleus ; physiology ; Drinking ; physiology ; Eating ; physiology ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; pharmacology ; Excitatory Amino Acid Antagonists ; pharmacology ; Male ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu ; physiology

Cyclosporin A is used to treat patients with immune-mediated diseases, chronic diseases requiring organ transplantation, or malignancies. These conditions often require higher cyclosporin A doses, which may be toxic to the central nervous system. Fentanyl is also used in clinical conditions that have a risk of hypoxic neurosusceptiblity, which suggests that the drug may be a neuroprotective agonist against brain ischemic injury. Fentanyl is an opioid agonist and appears to play an important role in regulating the excitability of the hippocampus under electroconvulsion. In this study, the effects of fentanyl on modulating cyclosporin A-induced neurotoxicity was investigated. Treatment with 3 micrometer of cyclosporin A was found to reduce the electroconvulsive activity threshold. Fifty ng/mL of fentanyl reduced the electroconvulsive activity, and 1 micrometer of DAGO ([D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin) also decreased the electroconvulsive activity. Fifty ng/mL of fentanyl was also found to reduce cyclosporin A-induced electroconvulsive activity. Although cyclosporin A neurotoxicity may be observed in various conditions, the opioid effect of neuroprotection may be involved in an interrelated mechanism. The exogenous opioid agonist suppressed cyclosporin A-induced electroconvulsive activity. Furthermore, there may be a functional anticonvulsant effect on cyclosporin A-induced neurotoxicity with an increased opioid agonist concentration.
Analgesics, Opioid/*pharmacology ; Animals ; Culture Techniques ; Cyclosporine/*pharmacology ; Dose-Response Relationship, Drug ; Electrophysiology ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology ; Female ; Fentanyl/*pharmacology ; Hippocampus/*drug effects/physiopathology ; Neuroprotective Agents/*agonists ; Rats ; Rats, Sprague-Dawley