Biomedical subjects

A L Riley

Publications and source records attributed to A L Riley.

At least 37 records · Page 2Linked to original sources

PubMed1993

An assessment of the interaction between cholecystokinin and the opiates within a drug discrimination procedure.

Recently, cholecystokinin (CCK) has been reported to antagonize a variety of opiate-induced effects, including nociception, body shaking, thermoregulation, and locomotion. Consistent with these results, a number of CCK antagonists potentiate the opiates in a range of behavioral and physiological assessments. The present study further examined the interaction between CCK and the opiates within the conditioned taste aversion baseline of drug discrimination learning, a design that utilizes the stimulus properties of the drug to control consummatory behavior. Specifically, animals injected with CCK prior to saccharin-LiCl pairings and the CCK vehicle prior to saccharin alone rapidly acquired the CCK-vehicle discrimination, avoiding saccharin consumption following the administration of CCK and consuming the same saccharin solution following the vehicle. Although the stimulus properties of CCK did not generalize to either naloxone or diprenorphine, morphine blocked and naloxone potentiated CCK's stimulus effects. These data are thus consistent with a physiological (rather than a pharmacological) interaction between CCK and the opiates.

Animals↗

PubMed1993

Cholecystokinin as a stimulus in drug discrimination learning.

Animals were trained to discriminate a relatively low dose of the octapeptide cholecystokinin (CCK) from distilled water within the conditioned taste aversion baseline of drug discrimination learning. Specifically, rats were injected with CCK (5.6 micrograms/kg) prior to the presentation of saccharin-LiCl pairings and with the CCK vehicle prior to the presentation of saccharin alone. After 10 conditioning trials (40 days), subjects acquired the discrimination, avoiding saccharin consumption following administration of CCK and consuming the same saccharin solution following the drug vehicle. Once the discrimination was acquired, a generalization function was determined for doses above and below that of the training stimulus. At doses below the training dose of CCK (i.e., 0, 3.2, and 4.2 micrograms/kg), subjects drank at control levels, whereas at the training dose and above (10 micrograms/kg) subjects significantly reduced consumption. That a relatively low dose of CCK can be used as a discriminative stimulus within a drug discrimination design may be important in that the procedure can now be used in the assessment of the pharmacological characteristics of CCK at a dose similar to that used in other behavioral assessments of the compound.

Animals↗

PubMed1993

Buprenorphine as a stimulus in drug discrimination learning: an assessment of mu and kappa receptor activity.

Using the conditioned taste aversion baseline of drug discrimination learning, different groups of animals were trained to discriminate either buprenorphine or morphine from distilled water. Specifically, animals were injected with buprenorphine or morphine prior to a saccharin-LiCl pairing and the drug vehicle prior to saccharin alone. By the fifth conditioning trial, animals differentially consumed saccharin on the basis of administration of the drug or its vehicle. In subsequent generalization tests, buprenorphine stimulus control generalized completely to the mu agonist morphine in four of the five subjects tested, while morphine stimulus control completely generalized to buprenorphine in two of five subjects and partially generalized in the remaining three. Buprenorphine failed to generalize to the relatively selective kappa antagonist MR2266 and the broad-based antagonist diprenorphine. Morphine also failed to generalize to MR2266, but did generalize to diprenorphine. That morphine and buprenorphine displayed some degree of cross-generalization suggests that these compounds share some stimulus property, presumably their agonist activity at the mu receptor, and that the mu activity of these compounds was used in the establishment of the discrimination, a conclusion supported by the fact that compounds with mu antagonist activity (e.g., naloxone, MR2266) blocked both buprenorphine and morphine stimulus control. That buprenorphine failed to generalize to compounds with kappa antagonist activity suggests that animals trained to discriminate buprenorphine from its vehicle do not use the kappa antagonist activity of the drug in the establishment of the discrimination. The basis for the differential ability of various receptor subtypes to mediate the discriminative properties of compounds with mixed receptor activity was discussed.

Animals↗

PubMed1992

Naloxone as a stimulus in drug discrimination learning: generalization to other opiate antagonists.

Nonopiate dependent animals were trained to discriminate the opiate antagonist naloxone (1 mg/kg) from distilled water within the conditioned taste aversion baseline of drug discrimination learning. Specifically, rats injected with naloxone prior to a saccharin-LiCl pairing, and with its vehicle prior to saccharin alone, rapidly acquired the drug discrimination, avoiding saccharin following the administration of naloxone and consuming saccharin following its vehicle after only three conditioning trials. Once the discrimination was acquired, generalization tests revealed that the opiate antagonists diprenorphine and naltrexone and the mixed opiate agonist/antagonist nalorphine completely generalized to the naloxone cue at doses of 1.8, 5.6 and 18 mg/kg, respectively. That discriminative control was established with a low dose of naloxone (i.e., 1 mg/kg) and other compounds with opiate antagonist activity generalized to the naloxone cue suggest that the stimulus effects of naloxone were likely mediated through the opiate receptor. Because each of these compounds are reported to bind to the mu receptor (with varying affinities and varying degrees of selectivity), the stimulus properties of naloxone are likely mediated at this specific receptor subtype.

Animals↗

PubMed1992

Antagonism of drug discrimination learning within the conditioned taste aversion procedure.

Animals injected with morphine prior to the presentation of a saccharin-LiCl pairing and the morphine vehicle prior to saccharin alone rapidly acquired the drug discrimination, avoiding saccharin following the administration of morphine and consuming saccharin following its vehicle after only four conditioning trials. Once stimulus control was established, the opiate antagonist naloxone (1 mg/kg) was administered prior to morphine in a test of its ability to antagonize the morphine stimulus. Pretreatment times ranged from 10 to 180 min. Naloxone antagonized the stimulus properties of morphine for all subjects, although there were individual differences in the onset, duration (time course) and degree of antagonism. Together with the rapid acquisition typically reported in this design, the fact that antagonism was demonstrated in the present study suggests that the conditioned taste aversion procedure may be useful in the general assessment of drug discriminations.

Animals↗

PubMed1992

Diprenorphine as a stimulus in drug discrimination learning.

Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate diprenorphine from distilled water. In subsequent generalization tests, the opiate antagonists naltrexone and naloxone and the mixed opiate agonist/antagonist nalorphine substituted for the diprenorphine stimulus in a dose-dependent manner, while the opiate agonist morphine and the nonopiate pentobarbital failed to substitute even at the highest doses tested. That a range of opiate antagonists substituted for the diprenorphine stimulus (and an opiate agonist and a nonopiate failed to substitute) suggest that diprenorphine's antagonist properties may mediate the discrimination, presumably by blocking endogenous opiate activity. The ability of these drugs to substitute for the diprenorphine stimulus may also be a function of this receptor activity. The differences in the specific generalization patterns reported in the present assessment and those of earlier reports were discussed.

Animals↗

PubMed1992

Effect of Ro 15-4513 on ethanol-induced conditioned place preference.

The benzodiazepine receptor inverse agonist Ro 15-4513 reverses a number of ethanol's effects, including its reinforcing properties as measured through self-administration. The present study examined the effect of this putative ethanol antagonist in a place conditioning design that has been shown to be sensitive to ethanol's rewarding properties in mice. Using an unbiased differential conditioning procedure, DBA/2J mice received, on alternate days, pairings of a distinctive floor stimulus (CS+) with either ethanol (2 g/kg), Ro 15-4513 (3 mg/kg), or a combination of ethanol and Ro 15-4513. On alternate days, a different distinctive floor stimulus (CS-) was paired with vehicle. Under these conditions, ethanol produced a conditioned place preference that was unaffected by Ro 15-4513. Ro 15-4513 alone did not produce either a place preference or aversion. Ro 15-4513 did produce reductions in locomotor activity during conditioning, indicating it was behaviorally active. These results indicate that a dose of Ro 15-4513 that alters general activity does not affect ethanol reward.

Animals↗

PubMed1991

Failure of cholecystokinin to precipitate withdrawal in morphine-treated rats.

In a test of the possible antagonistic interaction between cholecystokinin (CCK) and morphine, morphine-dependent rats were injected with one of three doses of CCK or with naloxone immediately following the consumption of a novel saccharin solution. Whereas opiate-dependent rats injected with the opiate antagonist naloxone acquired an aversion to the saccharin solution (and displayed a dramatic weight loss), CCK was without effect. These data were discussed in relation to the possible pharmacological antagonism between CCK and the opiates.

Animals↗

PubMed1991

Cocaine-induced taste aversions: effect of route of administration.

Female Long-Evans rats were given 20-min access to saccharin followed by either intraperitoneal (IP) or subcutaneous (SC) cocaine (18, 32 or 50 mg/kg) or vehicle. Aversions induced by IP-administered cocaine were relatively weak, with subjects at all doses decreasing consumption by only 35% after four conditioning trials. On the other hand, aversions induced by SC-administered cocaine were robust, with subjects at the two highest doses (32 and 50 mg/kg) decreasing saccharin consumption by 95 and 98%, respectively, on the final aversion test. Although several possibilities exist for the differential ability of IP and SC cocaine to induce taste aversions (e.g., longer duration of action with SC cocaine and the convulsant property of IP cocaine), the basis for this difference remains unknown. A secondary finding was the effect of route of administration on body weight. While all subjects receiving IP cocaine maintained or increased in body weight, subjects receiving the two highest doses of SC cocaine decreased in body weight by 3 and 5%, respectively. The differential effect of IP and SC cocaine on body weight may be due to cocaine's action on drinking and feeding or cocaine's leptogenic property. Independent of the mechanism underlying the differential ability of IP and SC administration to induce taste aversions and affect body weight, it is clear that route of administration may play an important role in the effects of cocaine.

Animals↗

PubMed1991

The effects of food schedule adaptation on the ability of naloxone to suppress the acquisition of schedule-induced polydipsia.

Naloxone suppressed the acquisition of schedule-induced polydipsia (SIP) in rats given no previous exposure to the feeding schedule. Adaptation to the feeding schedule prior to SIP acquisition attenuated this suppression. Specifically, water consumption, bout probability, licks/bout and maximum lick rates during the interpellet interval (IPI) were significantly increased by adaptation. Although adaptation attenuated the suppressive effects of naloxone on SIP, this attenuation was not complete. Adapted, naloxone-treated subjects displayed both decreased water consumption and bout probability as compared to distilled water-treated controls. Unlike the effects of adaptation on naloxone's suppression of SIP, adaptation completely eliminated naloxone's suppression of feeding. That adapted subjects ate at control levels while still displaying a lower level of SIP suggests that the suppressive effect of naloxone on the acquisition of SIP is not an indirect effect of naloxone on feeding, but rather a direct effect of naloxone on developing SIP. Given that naloxone has a general suppressive effect on drinking (including SIP), what remains to be determined is why naloxone has no effect on established SIP. Possible explanations for this are discussed.

Adaptation, Psychological↗

PubMed1991

Drug discrimination using a conditioned taste-aversion paradigm in rhesus monkeys.

The development of drug discrimination was assessed in rhesus monkeys using the conditioned taste-aversion paradigm. Monkeys were initially trained to respond under a fixed-ratio 30-response schedule of food-pellet delivery to assess the rate-decreasing effects of alprazolam (0.03 to 3 mg/kg, i.m., 60 min presession). Alprazolam decreased responding at doses greater than 0.1 mg/kg. Discriminative stimulus effects of alprazolam were then assessed by giving 0.03 mg/kg before sessions in which 1.8 mEq/kg lithium chloride was given immediately after the session (alprazolam/lithium session). On intervening days, saline was given before and after the session (saline/saline session). Rates of responding decreased over successive alprazolam/lithium sessions and also during the saline/saline session that immediately followed an alprazolam/lithium session. During subsequent saline/saline sessions, rates of responding returned to levels near baseline rates within two to four sessions. The discriminative stimulus effects of alprazolam were then assessed by giving 0.1 mg/kg before sessions in which 1 mg/kg d-amphetamine was given immediately after the session (alprazolam/d-amphetamine session). Rates of responding decreased during subsequent alprazolam/d-amphetamine sessions in drug-experienced monkeys, but did not decrease during intervening saline/saline sessions. These findings demonstrate that drug stimuli associated with postsession drug injections can rapidly develop control over behavior and suggest that similar methods be explored in the assessment of drug discrimination.

Alprazolam↗

PubMed1990

The effects of Ro 15-4513 on ethanol-induced taste aversions.

Ro 15-4513 is an imidazobenzodiazepine that has been reported to block a range of behavioral effects of ethanol. In the present experiments, the effects of Ro 15-4513 were assessed on the acquisition of an ethanol-induced conditioned taste aversion. Specifically, rats were given a novel saccharin solution to drink followed by an injection of one of a range of doses of Ro 15-4513 (0.5 and 1.0 mg/kg, Experiment 1A, and 2.0 and 3.0 mg/kg, Experiment 1B) and an injection of ethanol (1.75 g/kg). Ro 15-4513 failed to block the acquisition of the ethanol-induced taste aversion. Possible reasons for this failure were discussed.

Animals↗

PubMed1989

Conditioned taste aversions as a behavioral baseline for drug discrimination learning: an assessment with phencyclidine.

When PCP was given prior to the pairing of saccharin with LiCl (and the PCP vehicle prior to a nonpoisoned exposure to the same saccharin solution), rats rapidly acquired the discrimination, avoiding saccharin consumption following PCP and consuming saccharin following the vehicle after only three conditioning trials. Conversely, when the PCP vehicle was given prior to the saccharin-LiCl pairing and PCP prior to a nonpoisoned exposure to saccharin, other subjects avoided saccharin consumption following the vehicle injection and readily consumed saccharin after an injection of PCP. During dose substitution sessions, animals displayed greater drug-appropriate responding as the dose of PCP increased. When a range of doses of ketamine was given in place of PCP prior to saccharin access, subjects displayed dose-dependent PCP-appropriate responding. When a range of doses of d-amphetamine was substituted for PCP, subjects displayed vehicle-appropriate responding at all doses. The relative efficacy of the taste aversion procedure as a baseline for drug discrimination learning is discussed.

Animals↗

PubMed1988

Cholecystokinin potentiates the rate-decreasing effects of morphine on schedule-controlled behavior in rats.

In one component of a multiple schedule, responding (licking in rats) was reinforced under a fixed-ratio (FR 50) schedule of water presentation. In the other component, responding had no programmed consequences (timeout). Each session consisted of four 10-min timeout components alternating with four FR components. In general, increasing cumulative doses of morphine (3.2-18 mg/kg) produced a dose-dependent decrease in the overall rate of responding. In one subject, cholecystokinin (CCK) alone (10-32 micrograms/kg) produced dose-dependent decreases in rate in the first component, while in the other two subjects relatively little decrease in rate occurred. When these doses of CCK were given as a pretreatment before morphine, the decrease in overall response rate was greater than that found with morphine alone. This interaction was most noticeable at the lowest dose of morphine where CCK produced a dose-dependent "potentiation" of the rate-decreasing effects. Although the potentiation of CCK was not as evident at the intermediate doses of morphine, there were instances in which the rate-decreasing effects produced by the combination were greater than those expected from addition of the effects of CCK and morphine alone. In contrast, when naltrexone (1 mg/kg) was given as a pretreatment, little or no rate-decreasing effects were produced by the cumulative doses of morphine. Furthermore, pretreatment with naltrexone and the administration of a higher dose range of morphine indicated the dose-effect curve for morphine had shifted approximately 3/4 log-units to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

The differential effects of naloxone hydrochloride on the acquisition and maintenance of schedule-induced polydipsia.

Rats injected with the opiate antagonist, naloxone hydrochloride (10 mg/kg), 15 min prior to sessions in which they were given free food on a fixed time 75-sec schedule, displayed retarded acquisition of schedule-induced polydipsia relative to vehicle-injected subjects. Rats injected with naloxone after schedule-induced polydipsia had been acquired were unaffected, i.e., they continued to drink at control levels. Given that schedule-induced polydipsia has been considered non-opioid in nature, because of previous reports of its insensitivity to naloxone, the present report of differential effects of naloxone on the acquisition and maintenance of schedule-induced polydipsia suggests that some modification of this conclusion is necessary. Possible alternative mechanisms for these differential effects are discussed.

Animals↗

PubMed1986

Diminution of schedule-induced polydipsia after a long rest period.

Schedule-induced polydipsia was established in four food-deprived rats given daily hourly sessions in which a food pellet was presented once each min. Sessions were then discontinued for approximately six months. After this rest period, the daily sessions were resumed. Relative to the water intake during the last five sessions prior to the rest period, water intake during the first five sessions after the rest period exhibited a 55.5%, 10.3%, 32.0% and 29.6% decrement for the four rats, respectively. These results are discussed in terms of a sensitization view of schedule-induced polydipsia.

Animals↗

PubMed1986

A microcomputer-based system for stereotaxic coordinates in the rat brain.

In this report, the computer hardware and software used in the generation of a stereotaxic rat brain atlas are described. The atlas consists of sagittal and frontal sections drawn to the high-resolution page of the Apple II series computer. Brain architectural and macroscopic areas are represented by lines. Microscopic areas are represented by dots. The system employs a large data base to make available hundreds of brain areas on stereotaxic sections containing precise positional information of thousands of specific locations. For each display, the brain area is identified by name and by cross-hairs with digital display of stereotaxic coordinates. These coordinates may be referenced by earbar-zero or bregma. Other program options allow the printing of brain sections and a listing of available brain areas. Although designed for research in the neurosciences, the software may also be used for educational purposes.

Animals↗

PubMed1985

A software package for the microcomputer control and analysis of research on schedule-induced polydipsia.

This manuscript describes a software package called POLY which offers a range of routines designed to allow the user to set up, run and analyze data for research on schedule-induced polydipsia. The three major routines described are SETUP, RUN and ANALYSIS. The routines are flexible and give the user efficient control over the parameters of the research and the collection and analysis of the data. Although designed for research on schedule-induced polydipsia, the software can be used for other research purposes, requiring only changes in the support hardware.

Animals↗