Characterization of the discriminative stimulus effects of centrally administered morphine in the rat.

The discriminative stimulus effects of centrally administered morphine were characterized in rats trained to discriminate 3.0 mg/kg SC morphine from saline in a two-choice discrete-trial avoidance paradigm. The intracerebroventricular (ICV) administration of 0.

Effects of opiate antagonists and putative kappa agonists on unpunished and punished operant behavior in the rat.

The effects of naloxone and diprenorphine, opiate antagonists with different receptor-binding properties, and the putative kappa-receptor agonists, ketocyclazocine and ethylketocyclazocine (EKC), were studied on food-reinforced responding in rats. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response was punished by a brief electric footshock. Daily sessions were 1 h.

Characterization of stress-induced potentiation of opioid effects in the rat.

This study was designed to evaluate systematically the effects of stress on actions of exogenously administered opioids. Dose- and time-dependent analgesic (tail-flick) and thermic (core body temperature) effects of morphine and methadone were determined in unstressed rats and in rats exposed to the stress of restraint or a cold environment. To assess the role of the pituitary-adrencortical axis in stress-opioid interactions, tests were performed in hypophysectomized and pituitary-intact rats.

Differences in DMBA-induced mammary neoplastic responses in two lines of Sprague-Dawley rats.

It has been reported that female Sprague-Dawley rats obtained from a U.S. source and studied in the U.

Effects of naloxone, diprenorphine, buprenorphine and etorphine on unpunished and punished food-reinforced responding in the squirrel monkey.

The effects of naloxone and three oripavine derivatives, diprenorphine, an antagonist, buprenorphine, a mixed agonist-antagonist, and etorphine, an agonist, were examined on food-reinforced responding in squirrel monkeys. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response produced a brief electric shock to the tail. Daily sessions were 1 hr.

Repeated administration of naltrexone and diprenorphine decreases food intake and body weight in squirrel monkeys.

Although chronic administration of naloxone has been reported to reduce food intake and body weight in rats, there have been no comparable investigations using a nonhuman primate. We examined the effects of repeated injections of two long acting opiate antagonists - naltrexone and diprenorphine - on the ad libitum intake of a nutritional complete liquid diet and on body weight in squirrel monkeys. Naltrexone binds with highest affinity to the mu opioid receptor whereas diprenorphine binds with equally high affinity to several subtypes of opioid receptor.

Patterns of drinking in the rat following the administration of opiate antagonists.

Durations of drinking were recorded for water-deprived rats as they drank to satiety, following SC injections of naloxone (0.1-10.0 mg/kg), naltrexone (0.

Comparison of electrical resistance, bubble withdrawal, and stereotaxic method for cannulation of cerebral ventricles.

A comparison was made of three methods of lateral intraventricular (LV) cannulation in the rat brain. Rats in a control group (n = 8) were cannulated using traditional stereotaxic coordinates. In a second group (n = 8), electrical resistance was used to localize the ventricle and differentiate it from surrounding brain areas.

Complete, reversible, drug-specific tolerance to stimulation of locomotor activity by caffeine.

The development of tolerance to caffeine-induced stimulation of locomotor activity was evaluated in rats maintained chronically on average daily doses of 160 mg/kg or more of caffeine by the method of scheduled access to drinking water containing the drug. Dose-response curves were determined for caffeine (6.25-100 mg/kg) and d-amphetamine (0.

Effect of interval between neutron radiation and diethylstilbestrol on mammary carcinogenesis in female ACI rats.

Both radiation and diethylstilbestrol (DES) are carcinogens for the mammary gland of ACI female rats. When DES is given at about the same time as radiation, DES and radiation interact in a synergistic fashion particularly in regard to the number of mammary adenocarcinomas per rat. We have studied the effect of increasing the time interval between radiation and DES on the capacity of DES to enhance (promote?) radiation-induced mammary carcinogenesis.

The effects of naloxone, diprenorphine, and diazepam on responding suppressed by pre-shock and pre-food stimuli.

The lever-pressing of rats was reinforced with food according to a variable-interval 1-min schedule. In one group, occasional illumination of cue lights for 30-sec periods was followed by a brief electric shock; responding was suppressed during these periods. Naloxone (0.

Three-choice drug discrimination: phencyclidine-like stimulus effects of opioids.

To assess the commonalities and differences in the discriminative stimulus properties of phencyclidine (PCP) and psychotomimetic opioids, rats were trained to discriminate PCP (2.0 mg/kg), cyclazocine (1.0 mg/kg), and saline in a three-choice discrete-trial avoidance paradigm.

Further characterization of the three-choice morphine, cyclazocine and saline discrimination paradigm: opioids with agonist and antagonist properties.

Rats were trained in a three-choice morphine (3.0 mg/kg), cyclazocine (0.3 mg/kg) and saline discrimination using a discrete-trials avoidance procedure.

Effects of opiate antagonists and putative mu- and kappa-agonists on milk intake in rat and squirrel monkey.

The effects of a number of relatively pure opiate antagonists (naloxone, naltrexone, diprenorphine), and putative mu- (morphine, etorphine) and kappa- (ketocyclazocine, ethylketocyclazocine) receptor agonists on sweetened condensed milk intake were examined over a broad range of doses in non-deprived rats and squirrel monkeys. The antagonists consistently decreased milk intake in both the rat and squirrel monkey. There were, however, species differences: diprenorphine was 30 times more potent than either naloxone or naltrexone in the squirrel monkey, but was of similar potency in the rat.

Enhanced analgesic response to morphine in adult rats exposed to morphine prenatally.

Morphine exposure during development has been shown to produce fetal tolerance to morphine as measured by spontaneous activity only if a particular injection schedule is used. The present study was undertaken to compare the morphine-induced analgesic response in adult offspring of rats which had been injected during the last half of gestation on schedules known to produce fetal tolerance (5 mg/kg morphine at 6 hour intervals) versus a schedule known not to produce fetal tolerance (10 mg/kg morphine at 12 hour intervals). At 30 days postnatally the offspring of animals injected on these 2 schedules show no changes in their responsiveness to the analgetic effect of morphine as determined in the hot-plate test.

Properties of pentazocine as a discriminative stimulus in the squirrel monkey.

Squirrel monkeys were trained to discriminate i.m. injections of pentazocine (3.

Induction of mammary neoplasms in the ACI rat by 430-keV neutrons, X-rays, and diethylstilbestrol.

Mammary tumorigenesis was studied in female ACi rats after treatment with X-irradiation or neutron-irradiation, with or without diethylstilbestrol (DES) treatment. The mortality-corrected cumulative tumor rate based on all mammary neoplasms and the mortality-corrected incidence based on the first neoplasms only have been derived. In non-DES-treated animals, at the relatively high radiation doses studied, all dose-effect relationships were consistent with relative biological effectiveness (RBE) values slightly in excess of 10.

Effects of naloxone and diprenorphine on spontaneous activity in rats and mice.

The narcotic antagonist naloxone has been reported to decrease locomotor activity in the rat, presumably blocking endogenous opiate systems. Naloxone has a greater affinity for receptors which preferentially bind morphine and other opiate alkaloids as compared to receptors that bind endogenous opioid peptides. Diprenorphine, another pure opiate antagonist, binds with equal affinity to both receptor subtypes.

Analgesic effects of intraventricular morphine and enkephalins in nondependent and morphine-dependent rats.

The analgesic effects of i.c.v.

Stimulus properties of opioids with mixed agonist and antagonist activity.

The discriminative stimulus properties of opioids with mixed agonist and antagonist activity are heterogeneous in contrast to the relative uniformity of the stimulus properties of classical morphinelike agonists. Patterns of stimulus generalization to mixed agonist-antagonists are critically dependent on factors such as the particular drug used for training, dose of the training drug, and species of the experimental subject. Opioids can be divided into three broad categories on the basis of their patterns of stimulus generalization in rats and squirrel monkeys trained to discriminate saline from morphine, cyclazocine, or phenyclidine (PCP), and these categories predict the ease with which their stimulus effects can be blocked by nalozone or naltrexone.

Phencyclidine-like discriminative stimulus properties of opioids in the squirrel monkey.

The opioids SKF 10047, dl-cyclazocine, and dextrorphan have been shown to have phencyclidine (PCP)-like discriminative stimulus properties in the rat. In order to extend the generality of this observation, the stimulus effect of these and other opioids were evaluated in squirrel monkeys trained to discriminate between IM injections of saline and 0.25 mg/kg of PCP in a two-choice discrete-trial avoidance paradigm.