Positron emission tomography (PET) imaging of nicotine-induced dopamine release in squirrel monkeys using [F]Fallypride.

Background: Nicotine, the principal psychoactive tobacco constituent, is thought to produce its reinforcing effects via actions within the mesolimbic dopamine (DA) system. The objective of the current study was to examine the effect of nicotine on DA D/D receptor availability in the nonhuman primate brain with the use of the radioligand [F]fallypride and positron emission tomography (PET).

Methods: Ten adult male squirrel monkeys were used in the current study.

An intravenous self-administration procedure for assessing the reinforcing effects of hallucinogens in nonhuman primates.

Introduction: Self-administration procedures are the gold standard for investigating the reinforcing effects of drugs. The notable exception to good correspondence between laboratory self-administration studies and human drug taking behavior has historically been the classic hallucinogens.

Method: The present study used a well-established daily access procedure, followed by a novel intermittent access procedure, to investigate the reinforcing effects of LSD in baboons.

The Reinforcing Effects of Nicotine in Humans and Nonhuman Primates: A Review of Intravenous Self-Administration Evidence and Future Directions for Research.

Introduction: Cigarette smoking is largely driven by the reinforcing properties of nicotine. Intravenous (IV) self-administration procedures are the gold standard for investigating the reinforcing effects of psychoactive drugs. The goal of this review was to examine the results of published investigations of the reinforcing effects of nicotine measured using IV self-administration procedures in humans and nonhuman primates.

Effects of adolescent treatment with nicotine, harmane, or norharmane in male Sprague-Dawley rats.

The initiation of tobacco use occurs most often in adolescence and may be especially detrimental as the adolescent brain is undergoing substantial development. In addition to nicotine, there are over 9000 other compounds present in tobacco products, including the β-carbolines harmane and norharmane. The present study aimed to determine the long-term effects of adolescent exposure to nicotine (NIC), harmane (HAR), or norharmane (NOR) on locomotor activity, learning and memory, anxiety-like behavior, motor coordination, and monoamine/metabolite concentrations in the striatum and nucleus accumbens of male Sprague-Dawley rats.

Physical dependence on gamma-hydroxybutrate (GHB) prodrug 1,4-butanediol (1,4-BD): time course and severity of withdrawal in baboons.

Background: 1,4-Butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) pro-drug, with multiple commercial uses, and a drug of abuse. Although there are case reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated the physical dependence potential of 1,4-BD and characterized the time course of withdrawal.

Methods: Vehicle and then 1,4-BD were administered continuously 24 h/day via intragastric catheters in male baboons (Papio anubis, n=3).

Behavioral effects and pharmacokinetics of (±)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) after intragastric administration to baboons.

(±)-3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.

Self-administration of gamma-hydroxybutyric acid (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons.

Rationale: Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse.

Objective: Given the reports of abuse, and the ease at which GBL and 1,4-BD may be obtained, we investigated the reinforcing effects of GBL (n = 5) and 1,4-BD (n = 4) in baboons using IV self-administration procedures.

Methods: Sessions ran 24 h/day.

Metabolism and disposition of 3,4-methylenedioxymethamphetamine ("ecstasy") in baboons after oral administration: comparison with humans reveals marked differences.

The baboon is potentially an attractive animal for modeling 3,4-methylenedioxymethamphetamine (MDMA) effects in humans. Baboons self-administer MDMA, are susceptible to MDMA neurotoxicity, and are suitable for positron emission tomography, the method most often used to probe for MDMA neurotoxicity in humans. Because pharmacokinetic equivalence is a key feature of a good predictive animal model, we compared the pharmacokinetics of MDMA in baboons and humans.

Intravenous self-administration of γ-hydroxybutyrate (GHB) in baboons.

Background: Abuse of gamma-hydroxybutyrate (GHB) poses a public health concern. In previous studies, intravenous (IV) self-administration of GHB doses up to 10 mg/kg was not maintained in non-human primates under limited-access conditions, which was inconsistent with the usual good correspondence between drugs abused by humans and those self-injected by laboratory animals.

Methods: Self-administration of GHB was studied in 10 baboons using procedures standard for our laboratory to assess drug abuse liability.

Dissociation of alcohol-seeking and consumption under a chained schedule of oral alcohol reinforcement in baboons.

Background: Initiation and maintenance of compulsive alcohol drinking involves a sequence of behaviors which occur in the presence of environmental cues. Animal models using chained schedules of alcohol reinforcement may be useful for examining the complex interactions between cues and alcohol-seeking and -consumption.

Methods: Four baboons self-administered alcohol under a 3-component chained schedule of reinforcement; distinct cues were presented in the context of different behavioral contingencies associated with gaining access to 4% w/v alcohol (alcohol-seeking) and concluding with alcohol self-administration.

The value of nonhuman primates in drug abuse research.

The use of nonhuman primates (NHP) is invaluable for drug abuse research. The laboratory animals most closely related to humans are NHP. The phylogeny, anatomy, physiology, neurochemistry, and behavior of NHP are more similar to humans than other laboratory species.

Environmental cues, alcohol seeking, and consumption in baboons: effects of response requirement and duration of alcohol abstinence.

Background: Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions.

Methods: Alcohol drinking was established in 4 baboons.

Chronic intragastric administration of gamma-butyrolactone produces physical dependence in baboons.

Rationale: Abuse of gamma-hydroxybutyrate (GHB) and its precursors is a public health concern. Gamma-butyrolactone (GBL) is found in commercially available products and, when ingested, is metabolized to GHB.

Objective: The goal was to evaluate the physical dependence potential and behavioral effects of GBL.

Metabolism of gamma-hydroxybutyrate to d-2-hydroxyglutarate in mammals: further evidence for d-2-hydroxyglutarate transhydrogenase.

gamma-Hydroxybutyratic acid (GHB), and its prodrugs 4-butyrolactone and 1,4-butanediol, represent expanding drugs of abuse, although GHB is also used therapeutically to treat narcolepsy and alcoholism. Thus, the pathway by which GHB is metabolized is of importance. The goal of the current study was to examine GHB metabolism in mice with targeted ablation of the GABA degradative enzyme succinic semialdehyde dehydrogenase (SSADH(-/-) mice), in whom GHB persistently accumulates, and in baboons intragastrically administered with GHB immediately and persistently.

Involvement of gamma-hydroxybutyrate (GHB) and GABA-B receptors in the acute behavioral effects of GHB in baboons.

Rationale: Gamma-hydroxybutyrate (GHB) is used for the treatment of narcolepsy, but it is also a drug of abuse. The behavioral pharmacology of GHB is not well defined.

Objectives: The current study was conducted to characterize the behavioral effects of a range of GHB doses in baboons (N=4) and to evaluate whether a GABA-B receptor antagonist and a GHB receptor antagonist would block a behaviorally active dose of GHB.

Spontaneous and precipitated withdrawal after chronic intragastric administration of gamma-hydroxybutyrate (GHB) in baboons.

Rationale: gamma-Hydroxybuyrate (GHB) is a current drug of abuse that may produce physical dependence.

Objectives: The present study characterized the behavioral effects of chronic GHB in baboons (n = 4), and evaluated whether signs of withdrawal occurred (1) after administration of the GABA-B antagonist CGP36742 during chronic GHB administration (precipitated withdrawal) and (2) following discontinuation of chronic GHB administration (spontaneous withdrawal).

Methods: Water (vehicle) and then GHB was continuously infused via intragastric (IG) catheters.

Serotonergic-dopaminergic mediation of MDMA's discriminative stimulus effects in a three-choice discrimination.

(+/-)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a common drug of abuse that is often described as both a psychostimulant and a hallucinogen. Two-choice drug discriminations (i.e.