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Male rats display a conditioned preference to ejaculate with a female bearing an odor paired previously with copulation to ejaculation. The present study examined the role of endogenous opioid and dopamine systems in this preference. Male rats received saline, the opioid receptor antagoinst naloxone, or the dopamine receptor antagonist flupenthixol prior to 10 conditioning trials in a pacing chamber with an almond-scented female. On the final test, all males were injected with saline and given access to 2 females, 1 scented and the other unscented, in an open field. Only males injected with naloxone during training failed to manifest a conditioned ejaculatory preference. These findings suggest that activation of opioid, but not dopamine, systems during sexual interaction are necessary for conditioned ejaculatory preference in male rats. Keywords: opioids, dopamine, naloxone, flupenthixol, partner preference

The effects of the opioid antagonist naloxone were examined on the development of conditioned partner preference induced by paced copulation in female rats. In Experiment 1, ovariectomized, hormone-primed rats were conditioned to associate scented and unscented male rats with paced and nonpaced copulation, respectively. Female rats in Experiment 2 associated albino or pigmented male rats with paced or nonpaced copulation. Naloxone or saline was administered before each conditioning trial. During a final drug-free preference test, female rats could choose to copulate with either a pacing related or unrelated male. Saline-trained female rats in the paired group copulated preferentially with the pacing-related male rat, whereas naloxone-trained female rats did not show a preference. The authors concluded that opioids mediated the conditioned partner preference induced by paced copulation. Keywords: paced copulation, odors, sexual behavior and reward, conditioned partner preference, opioids

Sexual behavior in male rats induces a positive affect as evaluated by conditioned place preference (CPP). In addition, when females control or 'pace' the rate of sexual interaction, a clear CPP is also observed. The reward state induced by mating in male rats is blocked by the injection of the opioid antagonist naloxone. In the present experiment, a dose of 4 mg/kg of naloxone completely blocked the CPP induced in females by paced mating. It appears that a common opioid system is involved in the positive affect induced by sexual behavior in both male and female rats.

Research indicates that a reduction in opioid activity is not a substantial contributor to anorexia associated with aging. Both young people and elderly adults, in general, were found to be equally sensitive to naloxone's appetite suppression effects, suggesting that age-related anorexia has a different cause.

Experiments were conducted to evaluate the contribution of conditioning to tolerance to the meal-suppressive effect of naloxone (Nx) in rats. The results indicated (a) Nx suppresses consumption in a dose-dependent manner; (b) tolerance to this suppression of intake is 'contingent' (the rat must eat in conjunction with drug administration for tolerance to develop); (c) tolerance is displayed only in the context of environmental cues previously associated with Nx; (d) Nx-tolerant rats overeat when presented with cues previously associated with the drug; (e) Nx-tolerant rats display cross-tolerance to cholecystokinin. The results are consistent with C. X. Poulos and H. Cappell's (1991) 'homeostatic' theory of tolerance, as well as with the results of other experiments indicating that conditioning contributes to tolerance to many effects of various drugs.

The present experiment was designed to determine whether infusions of naloxone into specific brain sites can block sexual reinforcement as evaluated with the conditioned place preference procedure. Methylnaloxonium (5 microns g/cannula) was infused bilaterally either into the medial preoptic area (MPOA) or into the nucleus accumbens (NAC) of sexually experienced male rats. We chose the MPOA because it is important for sexual behavior, and several opioid peptides have been shown to modify sexual behavior when infused there. The NAC appears to be a critical structure for drug-induced reward. Methylnaloxonium blocked place preference produced by ejaculation after infusion into the MPOA without affecting sexual behavior. Infusion of the antagonist into the NAC did not reduce the reinforcing properties of ejaculation. These data suggest that the MPOA may be a site where sexual reward is produced.

Upon their first experience with milk, fetal rats express a stretch response that is similar to the postnatal behavior exhibited by infant rats at the nipple. Fetuses also posses a functional opioid system that is activated by prenatal milk exposure. The opioid receptor antagonist naloxone and the specific kappa antagonist nor-binaltorphimine blocked the stretch response and prevented the increase in rearlimb activity that is typically induced by milk. The mu antagonist beta-funaltrexamine blocked the stretch while permitting the expression of rearlimb activity. The kappa agonist U50,488 promoted rearlimb activity in the absence of milk, whereas the mu agonist (D-Ala squared, NMe-Phe to the fourth power, Gly to the fifth power-ol)-enkephalin (DAMGO) exerted little influence on fetal behavior. Fetuses pretreated with U50,488 stretched to nonmilk stimuli (saline or lemon), but fetuses pretreated with DAMGO did not. Opioid activation is part of a chain of events that culminates in the fetal stretch response and may be important in promoting milk ingestion during the newborn's first suckling episode.

Intravenous naloxone enhanced, and D-[Ala.sup.2]-Met-enkephalinamide (DALA) impaired, Pavlovian conditioned heart rate discrimination in rabbits (Oryctolagus cuniculus) during initial training trials, compared with saline; naloxone also delayed subsequent extinction of the discrimination. These effects of the pioid treatments on discrimination were abolished by parasagittal knife-cut lesions in the sublenticular substantia innominata that did not, themselves, impair discrimination. Both naloxone and DALA decreased the magnitude and altered the topography of bradycardiac conditioned responses, and the lesions also abolished these effects of the opioid treatments, but they did not alter the effect of naloxone to decrease bradycardiac orienting response magnitude. These findings suggest that fibers in the sublenticular area mediate specifically the effects of systemic opioids on associative functions during Pavlovian cardiac conditioning and extinction.

Previous studies with several different species have suggested that opioids and their receptors are involved in the mediation of the infant's vocal response to social isolation. In the case of the rat pup, 2 models have been hypothesized to relate opioids and the ultrasonic call emitted during social isolation. One model views the comforting effects of social contact as opioid mediated and the apparent distress of social isolation as analogous to opiate withdrawal. The 2nd model considers social separation as a stressor that recruits endogenous opioids. This article describes 3 experiments that tested both of these models in 7-10-day-old rat pups. In Experiment 1, morphine (0.04-0.40 mg/kg) decreased the rate of isolation calls in a dose-dependent, naloxone-reversible fashion. However, the decrease in calling rate was observed only at doses that decreased locomotor activity. Administration of the reversible opiate antagonist nalozone (0.05-5.0 mg/kg) did not alter the rate of calls during either 2- or 6-min isolation tests at either 24 or 32 [degrees]. In Experiment 2, the irreversible [mu] opioid receptor antagonist [beta]-funaltrexamine ([beta]-FNA) was administered into the lateral ventricle of 6-day-old pups. Again, no change in the rate of isolation calls was found, although sensitivity to morphine was markedly decreased, and [mu] (but not [delta] or [kappa]) receptors were decreased in selected brain regions by about 40%. In Experiment 3, in vivo receptor binding was used to directly investigate the availability of [mu] opioid receptors during social contact and social isolation. Pups injected with [sup.3.H-diprenorphine] showed relatively high levels of specific in vivo binding that followed the regional pattern of in vitro binding, but no effects of social isolation were apparent in the 5 brain regions assayed. Taken together, the consistent negative results with opiate receptor antagonists, as well as the inability to detect an alteration of in vivo binding, suggest that the [mu] opioid receptor is not an essential part of the rat pup's vocal response to social separation.

Mice pups were exposed daily to a stress-producing procedure (handling and saline injection) during the first 3 weeks of life. At 25 and 45 days of age, they were tested for differences in the tail-flick and hot-plate tests. The results indicate that chronic handling procedures during developmental stages can produce a long-lasting increase of the threshold for painful stimuli. This phenomenon is completely prevented by naloxone pretreatment and has enhancing effects on morphine analgesia, thus suggesting that postnatal handling can exert long-lasting interference on the sensitivity of some opioid receptor populations.

The barometric pressure (i.e. the total pressure of all gases in the air) decreases with increasing altitude. Chronic mountain sickness (CMS, also called Monge's disease) occurs at high altitudes because of the reduced pressure of oxygen in the air. CMS is accompanied by polycythemia (an increase in the number of red blood cells, to deliver more oxygen to the tissues) and is characterized by nausea, headache and insomnia. At high altitudes breathing patterns change and hyperventilation (an increase in breathing) is common. However, breathing by people with CMS often diminishes. The exact reason for this is unknown. When hypoxia occurs it causes an increase in respiration in an attempt to increase the amount of oxygen in the blood. This increase in ventilation in response to hypoxia is called a hypoxic ventilatory response (HVR). Previous reports have indicated that people living at high altitudes, with or without CMS, have a reduced HVR. CMS has been reported in Chinese who moved from the lowlands to Tibet. HVR was measured in 14 male Tibetans with CMS (all cigarette smokers) and in 11 without CMS (half of whom were smokers). Since obstructive lung disease is not uncommon in CMS, lung function tests were performed. Also, the effect of naloxone (a drug that blocks the effects of opioids, morphine-like substances produced in the body) on HVR was determined, since opioids reduce ventilation and HVR. Patients with CMS were found to have hypoventilation and a reduced HVR that did not respond to naloxone. Breathing air at a higher oxygen pressure caused a greater increase in ventilation in patients with CMS. Total lung capacity and residual volume in the lungs after exhaling were the same in CMS and control subjects. It is concluded that endogenous opioids are not implicated in causing CMS, and that hypoventilation, reduced HVR, and obstructive lung disease may account for the severe low oxygen content in blood observed in CMS. (Consumer Summary produced by Reliance Medical Information, Inc.)

Naloxone is an opiate antagonist drug, which can precipitate a withdrawal syndrome in opiate-dependent individuals. To see whether the acute onset of opiate withdrawal, induced by naloxone injection, could be overcome by co-medication with a barbiturate, 18 opiate-dependent patients (3 women, 15 men, aged 20-35 years) who had been addicted for 2 to 18 years were studied. Nine were randomly assigned to a naloxone group (A), and nine to a placebo group (B). They all received equal doses of morphine for two days, to ensure that no one began the study with withdrawal signs. On the third day, all received an injection of 100 milligrams of methohexitone (a barbiturate and general anesthetic). While anesthetized, they all received another injection of 400 mg methohexitone, immediately followed by injections of 10 mg naloxone (group A) or placebo (group B). When the narcotic effects of methohexitone had worn off, all were rated for withdrawal signs. Then, as a provocation test, 2 mg naloxone were administered to both groups. When the narcotic had fully worn off, the whole procedure was repeated. After this, all patients received equal doses of naloxone for 48 hours, and were observed for a week. When the methohexitone had worn off, Group B demonstrated only minimal withdrawal signs. However, in group B, the provocation test led to acute and severe withdrawal symptoms. In group A, after the barbiturate had worn off, and even after the provocation test, there were hardly any withdrawal signs. When both groups received naloxone for 48 hours after treatment, no increase in withdrawal symptoms was observed in either group. These results suggest a paradoxical pharmacological action of naloxone, since when it was administered with barbiturate anesthesia, high does prevented the onset of withdrawal signs. (Consumer Summary produced by Reliance Medical Information, Inc.)

A causal distinction is established in infant Norway rats between opioid - and nonopioimediated determinants of behavior. Contact influences are shown to be mediated by nonopioid pathways, whereas gustatory influences are shown to be opioid mediated. Specifically, naltrexone (0.5 and 1.0 mg/kg) did not at all diminish quieting exerted by contact with an anesthetized dam but completely reversed the quieting effects of morphine in isolated rats. Naloxone (5 mg/kg) did not affect the latencies with which nondeprived or 8-hr deprived rats 9, 12, 15, and 18 days of age attached to the nipples of anesthetized dams, nor did naloxone (5 and 10 mg/kg) cause any systematic change in nipple attachment in 10- and 18-day-old rats from the nipple when milk letdown was induced by oxytocin. Moreover, naloxone (5 and 10 mg/kg) did not reduce milk intake in Day-10 rats that, while suckling, received milk via a cannula placed in the posterior portion of the tongue at the level of the intermolar eminence or in rats that obtained milk directly from their awake mother. In contrast, milk intake was significantly reduced by naltrexone (0.25-1.0 mg/kg) in Day-10 rats that obtained milk (a) by licking it off a saturated substrate or (b) through an indwelling cannula located in the anterior portion of the lower jaw. (Milk delivered at this placement is thought to engage feeding systems by its taste and texture.) In a final set of experiments in Day-10 rats, intake of milk delivered via anterior jaw cannulae was reduced by naloxone (5 and 10 mg/kg) in rats that were either isolated, in contact with an anesthetized dam, or attached to her nipples. On the basis of resistance to naloxone and naltrexone administration, these experiments demonstrate that behavioral influences of the tactile (and possible olfactory) qualities of the mother are not mediated by opioid systems. Implications for understanding the means through which mothers can influence their young and the infantile mediators of these maternal influences are discussed.

The effects of morphine (30 mg/kg), naloxone (5 mg/kg), and morphine with naloxone on distress vocalizations and thermal nociception were examined in different strains of domestic fowl. Naloxone by itself did not significantly affect vocalizations or thermal nociception. Morphine produced a naloxone-reversible attenuation of vocalizations that was not strain dependent. Morphine produced a strain-dependent analgesic (Rhode Island Red strain) and hyperalgesic (White Leghorn and Cal-White strains) effect on tests of thermal nociception. Both the analgesic and hyperalgesic effects were reversed by naloxone. These opposite effects on thermal nociception may reflect the effects of selective breeding on opioid receptor subtype.

The role of naturally occurring opioids, which are morphine-like substances produced by the body, in the control of breathing is not clear. Naloxone is a drug that prevents the binding of opioids to specific sites on the cell membrane (receptors), and is used to study the actions of opioids. The effect of naloxone on the ventilatory response to hypercapnic hypoxia (an insufficient oxygen supply associated with increased levels of carbon dioxide in the blood) was assessed. In addition, the effect of naloxone on breathing patterns during hypercapnic hypoxia was examined. The study involved 21 healthy adults. Naloxone increased the ventilatory response to hypercapnic hypoxia. Eight subjects showed greater ventilatory responses to hypercapnic hypoxia after naloxone than the other subjects. These high responders also displayed greater ventilatory responses, breathing frequency, and average inspiratory flow during hypercapnic hypoxia before naloxone administration. These findings suggest that naturally occurring opioids normally help to regulate breathing during hypercapnic hypoxia. Their effects may be more evident in persons who have greater sensitivity to hypercapnic hypoxia. In addition, these actions of opioids may occur through effects on the central rather than peripheral nervous system. (Consumer Summary produced by Reliance Medical Information, Inc.)

Central naloxone injections were used to show that endogenous opioids in the ventral tegmental area (VTA) regulate consumption of palatable foods. Peripheral injections of naloxone were more effective in reducing the consumption of a sweet solution in normally fed rats than in animals maintained at 85% of their free-feeding body weight. A dose of 10 [microgram]/side naloxone injected into the VTA reduced consumption in normally fed rats, whereas a dose of 25 [microgram]/side did the same in food-restricted animals. The inactive isomer, (+) naloxone, did not reduce consumption; the effect has chemical specificity. Naloxone injected 0.5, 1.0, or 2.0 mm above the VTA did not reduce consumption; the effect has anatomical specificity. Naloxone effectively decreases the eating of palatable foods, but not eating for survival. This has important implications for the use of opioid antagonists in weight-loss programs.

This study is an investigation of the effects of stimulation of regions within and adjacent to the periaqueductal gray (PAG) matter. Eighty-five rats were implanted with 1 monopolar stimulating electrode into 1 of 5 loci. Potency of analgesia was evaluated by relative increases in tail-flick latencies after brain stimulation, and threshold current intensity was used to elicit analgesia. The ability of naloxone to reverse the stimulation-induced analgegia was also evaluated. Results replicate the previous finding of differential naloxone reversibility of eventral vs. dorsal PAG sites, but they do not support a regional distinction in the potency of analgesia induced. The results suggest that dorsal PAG sites are involved in a separate nonopiate pain-inhibitory system, whereas ventral sites are involved in an opiate system. These systems, however, do not respect the cytoarchitectural boundaries of the PAG because sites adjacent to the PAG elicit similar effects with a corresponding dorsal-ventral distinction.