1997 — 1998 |
Baker, Lisa E |
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. |
Dopamine D3 Receptors in Psychostimulant Discrimination @ Western Michigan University
Cocaine abuse and dependence remain a major health problem and social concern. In the last decade, the search for effective treatments for cocaine abuse has emphasized pharmacotherapeutic interventions. Despite the considerable progress toward an understanding of the neuropharmacological actions of cocaine and other psychostimulants, there remains no substantially effective pharmacotherapy for psychostimulant abuse. Recent investigations on potential candidates for pharmacotherapy have targeted pharmacological agents that have a preference for the dopamine D# receptor. The D3 receptor is highly concentrated in mesocorticoloimbic regions of the brain. Recent studies in laboratory animals have indicated that D3 receptors may be involved in the positive reinforcing effects of psychostimulants. D3- preferring agonists (e.g., 7-OH-DPAT) appear to enhance the reinforcing effects of cocaine while D3-preferring antagonists (e.g. (+)-AJ76, (+)-UH232 (-)-DS121) attenuate cocaine's reinforcing effects. D3-preferring agonists (7-OH-DPAT, (+)-PD128907) also exhibit stimulus generalization in rats trained to discriminate cocaine, although the D3-preferring antagonists do not substantially block the discriminative stimulus effects of cocaine or amphetamine. The primary goal of the proposed study is to utilize a more selective D3- preferring antagonists, U99194A, to investigate the role of D3 receptors in the discriminative stimulus effects of the psychostimulants, cocaine and amphetamine. U99194A will be tested for substitution, antagonism and potentiation in rats trained to discriminate cocaine or amphetamine from saline in a two-choice, water-reinforced drug discrimination procedure. In a separate experiment, rats will be trained to discriminate U99194A and stimulus generalization tests will be administered with several psychostimulants as well as with the D3-preferring antagonists (+)-UH232 and (-)- DS121. Finally, U99194A and the D2/D3 antagonist sulpiride will be tested in combination with (+)7OH-DPAT, (+)-PD128907 or U91356 in animals trained to discriminate cocaine or amphetamine, in an attempt to determine the importance of D2 vs D3 receptor modulation of the substitution of D3-preferring agonists for psychostimulants.
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2001 — 2003 |
Baker, Lisa E |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ghb: Discrimination and Effects On Learning @ Western Michigan University
DESCRIPTION: (provided by applicant) Gamma-hydroxybutyrate (GHB) abuse is a growing medical and social concern. Media attention has recently focused on the rampant recreational use of this substance among America's youth, and its notorious involvement in numerous drug-facilitated sexual assaults. The precursors of GHB (GBL and 1,4-BD) are found in some industrial solvents and also present a potential health hazard because their supply is not easily controlled. Despite the fact that GHB has been used for medicinal purposes in Europe for nearly 30 years and was available over-the-counter in the U.S. until 1990, the neurobehavioral consequences of GHB abuse are not well understood. Research on the neurochemical mechanisms underlying GHB's behavioral and subjective effects is imperative to understanding the abuse potential of this drug and ultimately to developing treatments for GHB abuse. Preclinical studies that assess these mechanisms are an essential component of this research. One objective of this proposal is to characterize further the neuropharmacological mediation of GHB's discriminative stimulus effects. This will be accomplished using both two-choice and three-choice drug discrimination techniques in rats. Because other researchers have had some difficulty maintaining adequate stimulus control with GHB, methodological parameters will be experimentally assessed to determine the optimal conditions for establishing and maintaining GHB discrimination. Additionally, because very little is known about GHB's effects on learning and performance in preclinical models, a second objective is to investigate the effects of GHB in several behavioral assays that involve operant conditioning in rats. The acute and chronic effects of GHB will be examined in rats: (a) responding a multiple schedule during 10-hr sessions; (b) initially acquiring lever-press responding with immediate and delayed reinforcement; (c) performing a conditional discrimination under a fixed-consecutive number (FCN) schedule with and without an external discriminative stimulus; (d) performing a delayed conditional discrimination (DCD); and (e) performing under a multiple schedule of reinforcement with punishment in one component. Behavior under these assays is sensitive to other abused drugs. Therefore, these assays may be of value in characterizing the effects of GHB.
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2015 |
Baker, Lisa E |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Preclinical Abuse Liability Screening of Designer Psychostimulant Mixtures @ Western Michigan University
? DESCRIPTION (provided by applicant): Athinone derivatives (bath salts) have similar neurochemical actions and produce comparable behavioral effects to other psychostimulants. In particular, these substances influence the activities of the brain reward pathways implicated in substance abuse and addiction. The proposed research plan will investigate 4-methylmethcathinone, also known as mephedrone (MEPH) and methylenedioxypyrovalerone (MDPV) alone and in combination with other drugs of abuse (e.g., cocaine, MDMA, amphetamine) and in combination with stress using the following validated preclinical assessments predictive of abuse liability: behavioral sensitization (BS), conditioned place preference (CPP), and drug discrimination (DD). The DD paradigm is a predictive model of the neurochemical actions responsible for the subjective effects of psychoactive drugs. As such, DD methods will primarily be utilized for the first specific aim to investigate the specific neuropharmacological actions involved in the discriminative stimulus functions of MEPH and MDPV and to determine if other psychostimulants potentiate the discrimination of these substances. For the second specific aim, BS and CPP methods will be utilized to determine if concurrent exposure to MEPH or MDPV with other psychostimulants enhances behavioral responses indicative of abuse liability. Finally, the third specific aim will implement BS and CPP methods to examine combined exposure to restraint stress and MEPH or MDPV in an effort to determine if the abuse liability of these substances is enhanced by the physiological correlates of stress. This research will contribute new information to the substance abuse literature and expand on current knowledge regarding the biobehavioral profile of methcathinone derivatives. As an AREA grant application, a major goal of this project is to engage students in research and discovery. Recent studies indicate that illicit methc Consistent with our university's mission to b learner centered, discovery driven, and globally engaged, students will participate in the design and implementation of experimental methodology, data analysis, manuscript preparation, and research poster presentations at conferences. Involving students in these research activities will strengthen and enhance the university's research environment. The opportunity to publish novel scholarly research will strengthen the students' prospective research careers.
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