2000 — 2001 |
Goodwin, Amy K |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Three Lever Discrimination of Mdma and Lsd in Rats @ Western Michigan University
The psychoactive compound (+)-3,4-methylenedioxymethamphetamine (MDMA) is a common drug of abuse popularly known as "ecstasy". There is a segment of the therapeutic community who claim MDMA may be a useful therapeutic tool because it promotes empathy and communication. However, MDMA is currently a Schedule I compound, making any medical use of it illegal. Moreover, it is likely that MDMA possesses neurotoxic properties. The psychoactive effects of MDMA are thought to be mediated through dopamine and serotonin neurotransmitter systems. MDMA is classified as both a "stimulant" and a "hallucinogen" because it shares subjective and physiological properties of both classes. We have established that the discriminative stimulus effects of MDMA can be differentiated by rats from those produced by the dopaminergically-mediated amphetamine cue. Thus, the specific aim of the present research proposal is to use a complex drug discrimination procedure to determine if the stimulus properties of MDMA can be differentiated from those of the serotonergically- mediated LSD cue. Twenty-four rats will be trained using a fixed-ratio 10 (FR 10) schedule of food reinforcement. Additionally, because drug discrimination research is time consuming, differential outcomes will be implemented to ascertain if this procedure facilitates the acquisition of the discrimination and/or the terminal accuracy of the acquired response. Differential outcomes will consist of pairing an exterioceptive stimulus (i.e., a light or tone) with each interioceptive stimulus condition (i.e., MDMA, LSD, or saline). The tone/light will be presented concurrently with the delivery of reinforcement. A control group will be exposed to these pairings on a random basis. Overall, it is important to accurately classify compounds with respect to abuse liability in order to identify and provide the most beneficial treatments; and in the case of MDMA, to evaluate therapeutic potential.
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1 |
2005 |
Goodwin, Amy K |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Self-Administration of Ghb, Gbl and 1,4-Bd in Baboons @ Johns Hopkins University
DESCRIPTION (provided by applicant): Gamma-hydroxybutyrate (GHB) is an endogenous substance found in the brain in mu/mol amounts and also a drug with well-documented misuse in humans. Since GHB became a Schedule I compound in 2000, the abuse liability of GHB precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) have begun to receive more attention. There have been few investigations into the reinforcing properties of GHB, GBL, and 1,4-BD, and the results have been inconsistent. Because GHB, GBL, and 1,4-BD have some sedative effects, the amount of time subjects have access to GHB, GBL, or 1,4-BD for self-injection may play a pivotal role when measuring the reinforcing effectiveness of these drugs. Thus, the current proposal will examine the reinforcing properties and abuse liability of GHB, GBL, and 1,4-BD in baboons using a 24 hr IV self-administration procedure. The behavioral effects of self-administered GHB, GBL, and 1,4-BD on food-maintained responding, spontaneous behaviors, and a fine motor task will also be characterized. The results of the proposed study will characterize the abuse liability of GHB, GBL, and 1,4-BD by use of a well-established method of abuse liability testing in non-human primates.
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0.945 |
2009 |
Goodwin, Amy K |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Hallucinogen Self-Administration in Baboons @ Johns Hopkins University
DESCRIPTION (provided by applicant): Although there has been a revived interest in the possible therapeutic effects of hallucinogens (Griffiths et al. 2006;Nichols 2004), such drugs are also popular drugs of abuse. Hallucinogens are generally considered to be physiologically safe (i.e., they do not result in physiological dependence nor do they cause disruption in cardiovascular, renal or hepatic functions) (Nichols 2004;O'Brien 2001). However, users of hallucinogens can experience hallucinogen persisting perception disorder (HPPD), fatal accidents resulting from distorted perceptions (e.g., attempting to fly), and psychoses-like side effects such as changes in cognitive functions and depersonalization (Abraham and Duffy 2001;Nichols 2004). In addition, use of hallucinogens may initiate the onset of psychosis or depression (Cohen 1960;Nichols 2004). The intravenous (IV) drug self-administration model has been used extensively to characterize the reinforcing effects of psychoactive compounds (Panlilio and Goldberg 2007). However, it has been generally accepted by the scientific community that while humans use LSD recreationally, laboratory animals do not self-administer it. The notion that laboratory animals don't self-administer LSD is likely based on data collected in the German lab of F. Hoffmeister in the 1970's, though the data was never published (Johanson and Balster 1978). Indeed, there are no peer-reviewed studies reporting the procedures used, nor the negative results of attempts to establish LSD as a reinforcer in laboratory animals. Accordingly, the conventional wisdom that hallucinogens do not function as reinforcers in laboratory animals is currently being reexamined. Fantegrossi and colleagues reported low levels of self-administration of the prototypical hallucinogens mescaline and psilocybin in rhesus monkeys (Fantegrossi et al. 2004). LSD also produces conditioned place preference in male rats (Meehan and Schechter 1998;Parker 1996). Thus, given that LSD is a popular drug of abuse, there are no published accounts of attempts to establish IV LSD as a reinforcer, LSD produces conditioned place preference in male rats (Meehan and Schechter 1998;Parker 1996), and other prototypical hallucinogens (i.e., mescaline and psilocybin) function as IV reinforcers in rhesus monkeys (Fantegrossi et al. 2004), we propose to examine the reinforcing effects of LSD using an IV self-administration model in baboons (a species with phylogenetic proximity to humans). PUBLIC HEALTH RELEVANCE: Although there has been a revived interest in the possible therapeutic effects of hallucinogens, such drugs are also popular drugs of abuse with the potential for adverse effects. An examination of the reinforcing effects of LSD in baboons is clinically relevant to the therapeutic use of these compounds, as well as the potential treatment for the abuse of these compounds.
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0.945 |