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Biomedical subjects

S D Comer

Publications and source records attributed to S D Comer.

30 records · Page 2Linked to original sources
PubMed1996

Combined effects of buprenorphine and a nondrug alternative reinforcer on i.v. cocaine self-administration in rats maintained under FR schedules.

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial against buprenorphine (0.1 mg/kg) and concurrent access to either water or a glucose plus saccharin solution (G+S, 3% and 0.125% wt/vol) in rats self-administering intravenous (IV) cocaine (0.4 mg/kg per infusion) under fixed-ratio schedules (FR2, 8 or 32). One group had concurrent access to water and another group had concurrent access to G+S. After 3 consecutive days of stable cocaine self-administration, a single buprenorphine injection (0.1 mg/kg IV) was administered 30 min before the start of the experimental session for 3 consecutive days. To summarize the results, (1) the presence of an alternative non-drug reinforcer significantly reduced cocaine self-administration, (2) buprenorphine selectively decreased cocaine, but not water or G+S, self-administration; (3) the decrease in cocaine infusions by buprenorphine was greatest on the first day of buprenorphine administration; and (4) expressed as a percentage of baseline conditions, the combination of buprenorphine and G+S produced a greater decrease in cocaine self-administration than either buprenorphine or G+S alone. These results indicate that combined treatment with buprenorphine and concurrent access to a sweetened solution is a more effective strategy for reducing cocaine self-administration than either strategy alone.

Animals↗
PubMed1996

Oral caffeine pretreatment produced modest increases in smoked cocaine self-administration in rhesus monkeys.

Several recent studies have shown that caffeine potentiates the reinforcing, discriminative stimulus, and motor activating effects of cocaine in rats. The present study was designed to determine whether oral caffeine pretreatment would enhance the reinforcing effects of cocaine in rhesus monkeys trained to self-administer smoked cocaine base. The effects of oral caffeine pre-treatment (0, 100, or 200 mg) and fixed-ratio (FR) value on cocaine-base smoking were evaluated in four male rhesus monkeys. Monkeys responded on a lever under a fixed-ratio (FR) schedule (FR 128, 256, 512, 1024, 2048, or 4096) and then made five inhalations on a smoking spout to gain access to volatilized cocaine base (0.25 or 1.0 mg/kg per delivery) during daily experimental sessions. Twenty pellets [20 non-caffeinated (0 mg caffeine), ten non-caffeinated+ten caffeinated (100 mg caffeine), or 20 caffeinated (200 mg caffeine) pellets] were administered 30 min prior to experimental sessions. The lever FR value was held constant within each experimental session, but was increased after 3 consecutive days of stable responding. Although the number of smoke deliveries that was self-administered significantly decreased from FR 128 to FR 4096, it did not change as a function of cocaine dose across the range of FR values tested. However, the interaction between cocaine dose and caffeine pretreatment was statistically significant. Compared to 0 mg caffeine, three of four monkeys pretreated with 200 mg caffeine responded for a greater number of smoke deliveries when they were maintained on a cocaine dose of 1.0 mg/kg per delivery, but not 0.25 mg/kg per delivery. Thus, caffeine pretreatment can produce small, but statistically significant increases in smoked cocaine self-administration in rhesus monkeys.

Administration, Oral↗
PubMed1996

Amphetamine self-administration by humans: modulation by contingencies associated with task performance.

The effect of task performance feedback and associated monetary earnings on drug self-administration were evaluated using eight subjects in a residential laboratory setting. The hypothesis was that if subjects believed that d-amphetamine impaired performance and reduced monetary earnings, d-amphetamine self-administration would decrease. Subjects performed computer tasks every day: on certain days that they received capsules, subjects were given bogus feedback regarding their performance ("better" or "worse" than average). On sample days, subjects were required to take d-amphetamine (10 mg BID) or placebo (0 mg BID) capsules. On choice days, subjects could choose between either d-amphetamine or placebo. Subjects received feedback on their task performance on 2 sample days and 2 of 4 choice days. Subjects received no feedback on the remaining two choice days. When subjects received no feedback, they chose d-amphetamine over placebo 78% of the time, and when they were given better feedback messages, they chose d-amphetamine 87.5% of the time. In contrast, d-amphetamine self-administration decreased significantly to 25% when subjects were told that it impaired their performance on work tasks and resulted in reduced earnings. In reality, d-amphetamine had little effect on work task performance. However, compared to placebo, d-amphetamine significantly increased subjective ratings of "Stimulated" and "Good Drug Effect" and significantly decreased ratings of "Tired" and "Sleepy." These results demonstrate that d-amphetamine served as a reinforcer under conditions in which drug self-administration did not influence monetary earnings, but that d-amphetamine self-administration could be modified by feedback/monetary earnings. Thus, contingencies associated with performance have important implications for drug use in the workplace.

Adult↗
PubMed1996

Effect of fenfluramine on food intake, mood, and performance of humans living in a residential laboratory.

Five male and four female normal weight research volunteers, participating in 13-day residential studies, received oral fenfluramine (20, 40 mg) or placebo at 09:30 and 17:00. Food intake, performance, and subjective ratings were measured throughout the day. Carbohydrate intake was manipulated by providing lunch meals high (males: 120 g; females: 80 g) or low (males: 25 g; females: 16 g) in carbohydrate on 8 days; on the remaining days subjects self-selected lunch. Total caloric intake (approximately 2800 Kcal) did not differ among the low- and high-carbohydrate, and self-selected lunch conditions when subjects received placebo, indicating caloric compensation. Total carbohydrate intake was significantly less, however, when subjects consumed the low-carbohydrate lunch compared to the other lunch conditions. Fenfluramine significantly decreased total caloric intake (approximately 500 kcal) by decreasing meal size, not number, only when subjects consumed the low-carbohydrate lunch. Fenfluramine was only an effective anorectic drug when subjects consumed a lunch with fewer calories and a lower carbohydrate:protein ratio than self-selected baseline. Also, fenfluramine improved performance on a range of computer tasks and increased ratings of "Alert," "Friendly," and "Talkative," while decreasing ratings of "Tired" and "Irritable."

Adult↗
PubMed1995

Food deprivation affects extinction and reinstatement of responding in rats.

Food deprivation has been shown to increase the self-administration of a wide variety of drugs in a number of different species. However, the effects of food deprivation on other phases of drug taking have not been established. The purpose of the present study was to evaluate the effects of food deprivation on reinstatement of responding for cocaine. Rats trained to self-administer 0.2, 0.4, or 1.0 mg/kg cocaine intravenously (IV) under a fixed-ratio 1 schedule for the first 2 h during daily 7-h sessions were fed either before or after the experimental session. During hours 3-7, rats self-administered saline. Saline replaced cocaine in the infusion pumps at the beginning of hour 3 and a priming injection of either saline or cocaine (0.32, 1.0, or 3.2 mg/kg IV) was administered at the beginning of hour 4. The number of infusions that was self-administered was measured throughout the 7-h session. During hours 1 and 2 when cocaine was available, the number of infusions was inversely related to cocaine dose. During hour 3, rats typically self-administered several infusions of saline, which gradually decreased to near-zero levels by hours 4-7 (extinction responding). A priming injection of cocaine administered at the beginning of hour 4 reinstated responding in a dose-related manner. The magnitude of extinction responding during hour 3 and reinstatement of responding during hour 4 were similar regardless of cocaine maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of food deprivation on cocaine base smoking in rhesus monkeys.

Studies have shown that both food deprivation and response cost have important influences on the magnitude of self-administration of a wide variety of psychoactive drugs. In an attempt to extend these findings to the smoked route of drug self-administration, the effects of food allotment and fixed-ratio (FR) value were evaluated in four male rhesus monkeys trained to smoke cocaine base. In the first phase of the experiment, monkeys were trained to self-administer experiment, monkeys were trained to self-administer smoked cocaine base under a chained progressive-ratio (PR), fixed-ratio (FR) schedule during daily experimental sessions. Monkeys were required to make 20 lever-press responses and then five inhalations on a smoking spout to obtain the first smoke delivery. The lever ratio than increased to 60, 140, 300, 620, 1260, 2540, and 4940 for each successive smoke delivery. The initial lever ratio value was reset to 20 at the beginning of each daily session. The body weights of three monkeys were determined under free-feeding conditions. Monkeys were then restricted to 100 g food and, when body weights had stabilized, the daily food allotment was increased to 150 g, approximately 210 g, or greater than 400 g (satiation). As the daily food allotment and body weight increased, the mean number of smoke deliveries decreased in two of three monkeys. In the second phase of the experiment, three monkeys were maintained under either food-satiated or food-restricted conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of concurrent saccharin availability and buprenorphine pretreatment on demand for smoked cocaine base in rhesus monkeys.

The effects of saccharin and the opioid partial agonist buprenorphine on cocaine base smoking were evaluated in five male rhesus monkeys. Monkeys completed a sequence of responding consisting of lever-press responses maintained under a fixed-ratio (FR) schedule followed by inhalation responses (FR5) on a smoking spout to gain access to a single delivery of volatilized cocaine base (1.0 mg/kg per delivery). Monkeys could receive a maximum of ten smoke deliveries per session. In the first experiment, either saccharin (0.03% wt/vol) or water was concurrently available under an FR1 schedule through a lip-operated drinking device. As lever FR values increased from 128 to 256, 512, 1024 and 2048, the number of cocaine smoke deliveries decreased. Cocaine intake was not statistically different when water versus saccharin was concurrently available. However, as cocaine consumption decreased, saccharin intake increased demonstrating that under these conditions, saccharin was substituting for cocaine as a reinforcer. On the first day that lidocaine replaced cocaine, all of the monkeys received the maximum number of smoke deliveries (ten) and saccharin intake increased. Lever-press responding gradually extinguished over days when lidocaine (1.0 mg/kg per delivery) was available with concurrent saccharin. In the second experiment, water was concurrently available with cocaine and buprenorphine (0.01 or 0.1 mg/kg) was administered intramuscularly (IM) 30 min before the start of the session. Although pretreatment with the lower dose of buprenorphine (0.01 mg/kg) had little effect on cocaine intake overall, individual differences in cocaine intake occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of buprenorphine and naltrexone on reinstatement of cocaine-reinforced responding in rats.

Reinstatement of responding previously maintained by cocaine was measured after noncontingent "priming" injections of cocaine, the opioid partial agonist buprenorphine, the opioid antagonist naltrexone and the opioid agonist etonitazene. The effects of pretreatment with buprenorphine, naltrexone or etonitazene on the reinstatement of responding produced by a priming injection of cocaine were also evaluated. The rats were trained to respond on a lever under a fixed-ratio 1 schedule to receive i.v. infusions of cocaine (1.0 mg kg-1 infusion-1) for the initial 2 hr during daily 7-hr sessions. Saline replaced cocaine at the beginning of hour 3, which resulted in an extinction of responding during the third hour and low levels of responding during the subsequent 4 hr of the session. Priming i.v. injections of cocaine (0.4-3.2 mg/kg), but not buprenorphine (0.025-0.4 mg/kg), naltrexone (1.6 and 3.2 mg/kg) or etonitazene (2.5 and 5.0 micrograms/kg), administered at the beginning of hour 4 of the session (i.e., during the extinction period), produced a dose-related reinstatement of responding. Pretreatment with either buprenorphine (0.025-0.4 mg/kg) or etonitazene (2.5 and 5.0 micrograms/kg), but not naltrexone (1.6 and 3.2 mg/kg), produced a dose-related suppression of the reinstatement of responding produced by 3.2 mg/kg of cocaine. These results indicate that 1) buprenorphine and naltrexone have little potential for producing reinstatement of responding in cocaine-maintained rats and 2) buprenorphine's effectiveness in preventing a reinstatement of responding produced by a cocaine priming injection may be related to its opioid agonist actions.

Animals↗
PubMed1993

Discriminative stimulus effects of BW373U86: a nonpeptide ligand with selectivity for delta opioid receptors.

Several opioid agonists were evaluated in pigeons trained to discriminate i.m. injections of sterile water from either the mu agonist morphine (5.6 mg/kg), the kappa agonist bremazocine (0.032mg/kg) or (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86; 0.56 mg/kg). Pigeons were trained to peak one of two keys on a fixed-ratio 20 schedule for food reinforcement. The pattern of substitution of mu, kappa and delta selective agonists in the three groups of birds suggested that the discriminative stimulus effects of morphine, bremazocine and BW373U86 were different; however, a component of the discriminative stimulus effects of BW373U86 appeared to be shared with morphine. Apparent pA2 values for naltrexone with morphine, bremazocine and BW373U86 were 7.6, 6.8 and 6.3, respectively. The apparent pA2 value for naltrindole with BW373U86 was 8.3. Naltrindole (10.0 mg/kg) produced a 3-fold shift to the right in the dose-effect curve for morphine but did not antagonize bremazocine. Although results from the substitutions experiments suggested that a component of the BW373U86 discriminative stimulus was mediated through mu opioid receptors, the fact that naltrindole was 1000-fold more potent and naltrexone was 30-fold less potent in antagonizing BW373U86 than morphine indicated that the discriminative effects of BW373U86 were also mediated through delta opioid receptors.

Amino Acid Sequence↗
PubMed1993

Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice.

A systemically active, nonpeptidic delta receptor-selective agonist, (+-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl) -3- hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), produced a brief, nonlethal convulsion in mice. The behavioral pattern of convulsion produced by pentylenetetrazol was similar to that produced by systemic administration of BW373U86. Although several episodes of convulsion occurred with pentylenetetrazol, BWB373U86 produced a single, brief episode. Naltrexone (10.0 and 100 mg/kg) and naltrindole (1.0, 3.2 and 10.0 mg/kg), but not midazolam (0.32 mg/kg), produced dose-dependent rightward shifts in the potency of BW373U86 to induce a convulsion. A dose of 3.2 mg/kg of midazolam completely eliminated convulsions induced by BW373U86. Midazolam (0.32 and 3.2 mg/kg), but not naltrindole (3.2 and 32.0 mg/kg), produced parallel rightward shifts in the pentylenetrazol dose-effect curve. Pretreatment with a single injection of BW373U86 (3.2, 10.0, 32.0 or 100 mg/kg) produced a dose-related reduction in the capacity of BW373U86 to induce a second convulsion. Recovery of sensitivity to BW373U86 did not return to control levels for up to 2 weeks after pretreatment with a single injection of 32.0 mg/kg of BW373U86. Naltrindole (3.2 mg/kg) administered within 1 hr, but not at 2 hr, after a pretreatment dose of 10.0 mg/kg of BW373U86 prevented the refractoriness (tolerance) induced by the single dose of BW373U86. These data suggest that the convulsions as well as the tolerance induced by BW373U86 were initiated through delta opioid receptors.

Amino Acid Sequence↗
PubMed1992

Clocinnamox: a novel, systemically-active, irreversible opioid antagonist.

The warm water (55 degrees C) tail-withdrawal procedure was used to assess the analgesic effects of the prototypic mu opioid agonists, morphine and fentanyl, in mice. Both drugs produced full analgesic effects under these conditions, which were dose-dependently antagonized by naltrexone. The pA2 values for naltrexone with morphine and with fentanyl were not significantly different. Low doses (e.g., 0.32 mg/kg) of clocinnamox [C-CAM.14 beta-(p- chlorocinnamoylamino)-7,8-dihydro-N-cyclopropylmethylnormorphin one mesylate] produced rightward shifts in the dose-effect curves for each drug, whereas high doses (e.g., 32 mg/kg) depressed the maximal analgesic response. In addition, it was observed that higher doses of C-CAM were required to produce a shift down in the fentanyl dose-effect curve than were required to produce a shift down in the morphine dose-effect curve, which suggests that fentanyl is more efficacious than morphine. The highest dose of C-CAM (32 mg/kg) antagonized the analgesic effect of morphine for up to 8 days. In contrast, the antagonist activity of naltrexone (100 mg/kg) against morphine lasted for only 2 days. Finally, when naloxone was administered simultaneously with 32 mg/kg C-CAM 2 days before determination of the morphine dose-effect function, the antagonist effect of C-CAM was prevented in a dose-dependent manner. Taken together, these results suggest that C-CAM may be producing its antagonist action at opioid receptors through a nonequilibrium mechanism.

Analgesia↗