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At least 19 recordsLinked to original sources
PubMed2007

Gabapentin does not reduce smoked cocaine self-administration: employment of a novel self-administration procedure.

Previously, we reported that gabapentin, a nonselective gamma-aminobutyric acid agonist, reduced 'positive' subjective effects of cocaine without reducing cocaine self-administration. We speculated that the self-administration procedure used in that study was not sensitive to subtle shifts in the reinforcing effects of cocaine. Thus, this study examined the effects of gabapentin maintenance on cocaine self-administration using a purchase-cocaine choice procedure. During this 48-day inpatient/outpatient study, nontreatment-seeking cocaine abusers (n = 12) were maintained on gabapentin (0, 600, 1200 mg/day); four doses of cocaine (0, 12, 25, 50 mg) were each tested twice under each gabapentin condition. All cocaine testing was conducted while participants were inpatients. Before the start of each session, participants were provided with 25 dollars (five 5 dollar bills, one for each choice opportunity) and smoked the 'sample' cocaine dose once. Subsequently, participants were given five opportunities to purchase the sampled dose of cocaine (at 5 dollars per dose) or to keep 5 dollars for that choice trial. Choice to self-administer cocaine increased significantly with escalating cocaine doses; gabapentin maintenance did not alter choice to self-administer cocaine. These results concur with findings from our previous investigations of gabapentin and with those from a clinical trial examining the effects of larger gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals. Together, the data indicate that gabapentin does not show promise as a treatment medication for cocaine dependence.

Adult↗
PubMed1992

Remoxipride, a specific D2 dopamine antagonist: an examination of its self-administration liability and its effects on d-amphetamine self-administration.

The self-administration liability of remoxipride, a specific dopamine D2 antagonist, by laboratory rats was evaluated using an intravenous self-administration paradigm. It was observed that remoxipride failed to support self-administration behavior across the three doses tested. In addition, remoxipride pretreatment attenuated d-amphetamine self-administration. The findings of the present study provide support for the notion that remoxipride appears to have functional similarity in self-administration paradigms as other D2 antagonists.

Animals↗
PubMed1993

Effects of intermittent buprenorphine administration on cocaine self-administration by rhesus monkeys.

In previous studies, daily buprenorphine administration significantly reduced cocaine self-administration by rhesus monkeys over 15 to 120 days (Mello et al., 1990, 1992). This report describes the effects of 60 days of intermittent buprenorphine (0.40 mg/kg) treatment once every 48 hr or 72 hr on cocaine and food self-administration by six rhesus monkeys. Cocaine (0.05 or 0.10 mg/kg/injection) and food (1-g banana pellet) self-administration were maintained on a fixed ratio 4, (variable ratio 16:S) reinforcement schedule. Intermittent buprenorphine treatment reduced cocaine self-administration significantly below saline treatment levels (P < .01). On the first day of buprenorphine treatment, cocaine self-administration averaged 53 and 60% below base line (P < .01-.0001). Cocaine self-administration remained significantly below base line on day 2 (P < .02-.0001) but usually returned to base-line levels by day 3. During buprenorphine treatment once every 48 hr, cocaine self-administration gradually increased over time in four monkeys (P < .001-.0005). These data suggest that intermittent buprenorphine treatment is less effective than daily buprenorphine treatment in reducing cocaine self-administration by rhesus monkeys. Food self-administration decreased by 23.6 and 12.7% from the saline base line during buprenorphine treatment every 48 and 72 hr, respectively. On the day of buprenorphine treatment, food self-administration was usually significantly lower than during the saline base line (P < .05-.0001), but usually returned to or exceeded base line levels by days 2 and 3. There were no significant changes in food self-administration over time with intermittent buprenorphine treatment every 48 hr.

Animals↗
PubMed2001

Self-administration cues as signals: drug self-administration and tolerance.

There is evidence that drug-associated exteroceptive cues elicit compensatory conditional responses (CCRs) that contribute to tolerance. The authors evaluated whether interoceptive, self-administration cues (SACs) similarly contribute to tolerance. In Experiments 1 and 2, the ataxic effect of ethanol was measured in rats that self-administered (SA) ethanol--by either oral consumption or intragastric infusion--and in rats that were yoked (Y) to these self-administrators. In both experiments, the ataxic effect of ethanol was more pronounced in Y than in SA rats. In addition, SA rats failed to display usual levels of tolerance when ethanol was administered in the absence of SACs and displayed a CCR of hypertaxia in response to SACs not followed by ethanol. The results of Experiment 3 indicate that the ataxic effect of intravenous heroin also was greater in Y than in SA rats. The findings suggest that SACs contribute to drug tolerance.

Animals↗
PubMed1975

Experimental models for the modification of human drug self-administration: Methodological developments in the study of ethanol self-administration by alcoholics.

Experimental studies of human ethanol self-administration are reviewed, and a description is provided of the procedural evolution that has oc-urred in the experimental study of the determinants of human ethanol self-administration. Human experimental models of alcoholism have been established within residential laboratories which permit chronic availability of ethanol to volunteer alcoholic subjects. Experimentation within such environments has progressed from observational and descriptive studies of experimental intoxication to studies that manipulate experimental variables so as to modify (reduce) ethanol self-administration by alcoholic subjects. To observe systematic effects of manipulated variables it has been necessary to develop sensitive baselines of ethanol self-administration. When ethanol intake has been relatively unrestricted, wide spontaneous fluctuations have made difficult the evaulation of manipulated variables. When a variety of restrictions on ethanol availability have been imposed, sensitive self-administration baselines have been established which have permitted the direct experimental assessment of some of the determinants of ethanol self-administration. Six methodological principles are suggested for enhancing the information yield of future research on the determinants of ethanol self-administration. The same general methodology is suggested for research with other varieties of drug self-administration.

Administration, Oral↗
PubMed2000

What we have learned about addiction from animal models of drug self-administration.

Self-administration of addictive drugs in laboratory animals has been widely used for decades as a tool for studying behavioral, neurobiological, and genetic factors in addiction. From such studies has come an enormous amount of information on brain mechanisms involved in addiction, on vulnerability factors in the addictive process, and on possible pharmacotherapeutic treatments for addiction. Modifications of the laboratory animal self-administration paradigm--including progressive ratio break-point models and the "reinstatement" model of relapse to drug-seeking behavior--are currently increasing our knowledge of incentive motivational factors in addiction and of the mechanisms underlying relapse to drug self-administration behavior.

Animals↗
PubMed2006

Accumbal neurons that are activated during cocaine self-administration are spared from inhibitory effects of repeated cocaine self-administration.

Hypoactivity of the accumbens is induced by repeated cocaine exposure and is hypothesized to play a role in cocaine addiction. However, it is difficult to understand how a general hypoactivity of the accumbens, which facilitates multiple types of motivated behaviors, could contribute to the selective increase in drug-directed behavior that defines addiction. Electrophysiological recordings, made during sessions in which rats self-administer cocaine, show that most accumbal neurons that encode events related to drug-directed behavior achieve and maintain higher firing rates during the period of cocaine exposure (Task-Activated neurons) than do other accumbal neurons (Task-Non-Activated neurons). We have hypothesized that this difference in activity makes the neurons that facilitate drug-directed behavior less susceptible than other neurons to the chronic inhibitory effects of cocaine. A sparing of neurons that facilitate drug-directed behavior from chronic hypoactivity might lead to a relative increase in the transmission of neuronal signals that facilitate drug-directed behavior through accumbal circuits and thereby contribute to changes in behavior that characterize addiction (ie differential inhibition hypothesis). A prediction of the hypothesis is that neurons that are activated in relation to task events during cocaine self-administration sessions will show less of a decrease in firing across repeated self-administration sessions than will other neurons. To test this prediction, rats were exposed to 30 daily (6 h/day) cocaine self-administration sessions. Chronic extracellular recordings of single accumbal neurons were made during the second to third session and the 30th session. Between-session comparisons showed that decreases in firing were exhibited by Task-Non-Activated, but not by Task-Activated, neurons. During the day 30 session, the magnitude of the difference in firing rate between the two groups of neurons was positively related to the propensity of animals to seek and take cocaine. The findings of the present study are consistent with a basic prediction of the differential inhibition hypothesis and may be relevant to understanding cocaine addiction.

Action Potentials↗
PubMed1989

Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration.

The reinforcing effects of diazepam (DZ), triazolam (TZ) and placebo were examined in eight male subjects with histories of sedative abuse. DZ (40 or 80 mg), TZ (1.0 or 2.0 mg) and placebo were each individually available for oral self-administration using a double-blind within-subject design. After an initial sampling exposure, subjects could self-administer a single dose of drug on each of 6 days by completing a progressively increasing bicycle riding requirement. All subjects initially self-administered DZ and TZ but a decreasing number of subjects continued to self-administer drugs on the remaining days; there was no difference between DZ and TZ in the total number of self-administrations. Placebo was self-administered only by one subject on two occasions. Performance measures showed that TZ produced greater memory impairment than DZ and that DZ produced residual psychomotor impairment on the next day. With repeated dosing, evidence of tolerance was seen for both drugs on psychomotor and memory performance and subject ratings of drug liking. A few modest correlations of drug self-administration and subject-ratings were obtained, suggesting some correspondence of subject verbal and drug self-administration behaviors, but these measures did not covary in a completely consistent manner.

Adult↗
PubMed1984

Effects of repeated methamphetamine administration on methamphetamine self-administration in rhesus monkeys.

The effects of prolonged exposure to high doses of stimulants on stimulant self-administration in rhesus monkeys have not been established. In the present experiment, rates of methamphetamine self-administration as well as the effects of methamphetamine on food-maintained responding were determined before and after a regimen of repeated methamphetamine injections. Increases in self-administration of some doses of methamphetamine as well as tolerance to the rate-decreasing effects of the drug on food-maintained responding were observed following the repeated injection regimen. The results suggest that while tolerance may develop to the rate-decreasing effects of the drug, there may be an increased sensitivity to its reinforcing properties. In addition, since this injection regimen has been shown in previous studies to deplete central monoamines, especially dopamine, the results suggest a role for these monoamines in these behavioral effects of methamphetamine.

Animals↗
PubMed1982

Schedule-induced cigarette self-administration.

Cigarette self-administration was studied in a controlled laboratory setting by automated recording of the various components of smoking behavior. The effects of intermittent scheduled monetary reinforcement presentation on cigarette smoking was determined in an attempt to demonstrate schedule-induced cigarette self-administration. Schedule-induced cigarette self-administration was indicated by changes in some of the topographical components of cigarette smoking behavior, e.g., puff frequency and mean puffs per cigarette, as a function of changes in the fixed interval value of a monetary reinforcement schedule. While the number of cigarettes smoked changed only slightly following changes in the FI value of the monetary reinforcement schedule, other components of cigarette smoking behavior, particularly puff frequency and mean puffs per cigarette, were significantly altered. Cigarette puffs were most likely to occur immediately following monetary reinforcement presentation or in the initial segment of the next fixed interval. The demonstration of schedule-induced self-administration in human adds another common factor found to influence infrahuman and human drug self-administration.

Behavior↗
PubMed1985

Concurrent heroin self-administration and intracranial self-stimulation in rats.

In a two-lever testing chamber, rats lever pressed for lateral hypothalamic brain stimulation or intravenous heroin reinforcers on a concurrent FR1 FR1 schedule of reinforcement. Responding for stimulation did not alter the rate of heroin self-administration, and responding for heroin caused increased responding for stimulation. Discontinuing heroin injections, or administering 3 mg/kg of naloxone, disrupted responding for both reinforcers, while changing the unit dose of heroin did not appreciably affect response rates for stimulation. This experiment demonstrates that rats are able to lever press during the period between successive self-administered heroin infusions, suggesting that the pausing normally seen between infusions is not due to debilitation, stereotyping, or sedation.

Animals↗
PubMed1981

History of drug exposure as a determinant of drug self-administration.

Drug self-administration is controlled, in part, by the subject's history of drug exposure. Although a history of drug administration is not necessary for many drugs to function as reinforcers, prior exposure can increase the likelihood that certain drugs, such as ethanol, will maintain behavior. While it has been demonstrated that physiological dependence is not necessary for a drug to function as a reinforcer, the conditions under which such dependence is maintained can control the later self-administration of the drug. Once drug-maintained behaviors are established, the particular drug that maintains behavior can influence the initial pattern of intake of a new drug and thus the dose of that drug that will maintain behavior. Additionally, under certain conditions, similarity between the discriminative stimulus effects of the drug that previously maintained behavior and those of a new drug can increase the likelihood that the new drug will function as a reinforcer. Finally, stimuli that have been paired with drug administration can powerfully control later drug-maintained behavior, the direction of such control being determined by the conditions under which such pairing occurred. In summary, both the type of drug with which a subject has experience as well as the contingencies governing that experience contribute to subsequent drug self-administration.

Animals↗
PubMed1976

Effect of unit dose and route of administration on self-administration of morphine.

Rats were implanted with intravenous or intragastric cannulas and allowed to self-administer morphine sulfate in doses of 0 (saline), 0.03, 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg/infusion. For the intravenous route the number of infusions decreased with increasing unit dose, while the amount self-administered was directly related to unit dose. However, for the intragastric route the number of infusions first increased and then decreased as unit dose was elevated, while the amount self-administered again increased with unit dose. Comparisons between routes showed that for intragastric subjects the number of infusions and amount self-administered both were lower at the two lowest doses but higher for all other doses. These results support the expectation that intravenous injection should produce more potent reinforcing effects than intragastric administration.

Animals↗
PubMed2005

Involvement of kappa/dynorphin system in WIN 55,212-2 self-administration in mice.

Self-administration procedures have not yet provided evidence that freely moving mice can reliably acquire and maintain an operant behavior to self-administer cannabinoid agonists. The aim of the present work was to establish a model of cannabinoid operant intravenous self-administration in freely moving mice given the relevance of this species for the use of genetically modified animals. In addition, the possible involvement of the kappa/dynorphin system in cannabinoid self-administration was evaluated by using pro-dynorphin knockout mice. Outbred CD1 wild-type mice as well as pro-dynorphin knockout and wild-type mice were trained to self-administer the cannabinoid receptor agonist WIN 55,212-2 under an FR1 schedule of reinforcement. Two cannabinoid training doses (6.25 and 12.5 microg/kg/infusion) were used in the acquisition studies in outbred mice. Animals acquired a reliable operant responding to self-administer WIN 55,212-2 (12.5 microg/kg/infusion), but required as many as 15 sessions to attain this behavior. Interestingly, when a previous injection of WIN 55,212-2 (0.1 mg/kg, i.p.) was administered in the home-cage 24 h before the first session, mice acquired operant responding for cannabinoid self-administration by the fourth session. When the kappa-opioid agonist antagonist nor-binaltorphimine (5 mg/kg s.c.) was administered 4 h before the first session, the time required to acquire a reliable cannabinoid self-administration was also significantly reduced. Finally, a shift to the left in the dose-intake curve to self-administer WIN 55,212-2 was observed in pro-dynorphin knockout mice when compared to wild-type mice. These results indicate that the activation of the kappa/dynorphin opioid system after WIN 55,212-2 administration could counteract cannabinoid rewarding effects.

Animals↗
PubMed1988

Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys: substitution during phencyclidine self-administration and withdrawal.

Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (+/-) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (+/-)-NANM were reinstated in subsequent replications of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗