1997 — 2000 |
Glowa, John R. |
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. |
Determinants of Drug Effects On Drug Maintained Behavior @ Louisiana State Univ Hsc Shreveport
Drug-maintained behavior serves as an appropriate model to assess potential treatments for drug abuse. Recent studies have shown that agonist treatments can decrease responding maintained by cocaine, or opiates. These effects have been shown to be persistent, and without deleterious consequence. They are interpreted as a substitution effect, similar to that expected of methadone for heroin abuse and nicotine patches for tobacco abuse. Confirmation of this notion may lead to the development of agonist treatments for other forms of substance abuse. The utility of this approach is that compliance is expected to be greater than that seen with antagonist-based treatments. in addition, agonists only decrease drug-intake, while increases in drug intake have been observed with antagonists. Preliminary clinical reports suggest that agonists exhibit efficacy in humans. Nevertheless, this form of treatment deserves more study before being implemented. One reason is that other forms of treatment may be more efficacious. For example, some studies have shown that providing access to non-drug reinforcers can also decrease drug- maintained responding. Another reason is that few studies have addressed the therapeutic ratio for agonist effects, nor the range of conditions under which drug-seeking can be decreased. The current studies are designed to more fully assess the nature of agonist treatments on drug- maintained behavior. In doing so, several issues related to obtaining a better understanding of determinants of the reinforcing efficacy of drugs will be addressed. Traditional methods of determining the reinforcing effects of drugs have been limited to either the extent to which different doses will support higher ratio requirements,or the assessment of rates of responding maintained by different doses of a drug. While the former has been criticized for a lack of stability, the latter is rarely accomplished due to the large amount of data required. Recently, it has been suggested that these two indices can be combined to describe a single function relating reinforcing effects of drugs behavioral output per dose. This possibility would allow a using a more rapid assessment of agonist effects on drug- maintained behavior, if limited data sets can adequately describe this function. The initial studies of the proposal seek to address this issue by comparing these measures of reinforcing efficacy of drugs, using cocaine and fentanyl. Subsequent studies will use these measures to address: l) the nature of the ability of agonists to decrease drug- maintained responding, 2) the relationship between reinforcing efficacy of the treatment drug and the drug for which treatment is sought, 3) the relative abilities of treatment drugs to decrease food- and drug- maintained responding, 4) the ability of agonists from other classes of drug reinforcers as well as receptor-specific agonists and antagonists, to affect drug-maintained responding, 5) how these measures compare with other measures of relative reinforcing efficacy of drugs, and 6) ways in which agonist treatment can be used to permanently decrease drug- maintained behavior.
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0.907 |
1997 — 1998 |
Glowa, John R. |
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. |
Mechanisms of Inhalant Abuse @ Louisiana State Univ Hsc Shreveport
DESCRIPTION: (Applicant's Abstract) Inhalants are the only major class of abused drugs that are not regulated in the United States. Inhalant abuse is on the rise, particularly among young adolescents, and little is known of the consequences of this behavior. Because of the unrestricted availability of inhalants, often as common household items, there is growing concern that they may serve as a 'gateway drug' for other forms of drug abuse. Given the large number of inhalants available, it is imperative to explore ways of identifying those with abuse potential. Although methods have been developed to screen for abuse potential, they have not been applied to inhalants. Presumably this is because of the difficulties in arranging inhalation as a route of administration in experimental animals. Recent advances in vehicle preparations for inhalant-like anesthetics such as propofol and isoflurane provide a means to apply intravenous self-administration techniques to the study of the abuse potential of inhalants. Promising pilot data appears to confirm that these agents support behavior that leads to their delivery. The initial phases of this project are designed to screen a wide range of inhalants for behavioral activity. The next phase of the project will directly determine the abuse potential of behaviorally active agents using self-administration techniques. The initial phase will rank order the abuse potential of compounds actively self-administered using two techniques that have been successfully applied to assess the abuse potential of other types of agents. If time permits, this project will also determine the effects of drug pretreatment on inhalant-maintained performances, in order to more fully evaluate their ability to alter measures of reinforcing efficacy of inhalants. In addition to the direct benefits of rank ordering the extent to which various inhalants are likely to be abused, this project characterizes a new class of drugs of abuse, and as such, potentially adds to our knowledge of factors associate with drug abuse in general.
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0.907 |