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Determinant of reinforcing efficacy ...

Wee, Sunmee.

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Determinant of reinforcing efficacy of phenyltropanes: Onset of dopamine transporter occupancy.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Determinant of reinforcing efficacy of phenyltropanes: Onset of dopamine transporter occupancy./
作者:	Wee, Sunmee.
面頁冊數:	106 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2533.
Contained By:	Dissertation Abstracts International66-05B.
標題:	Health Sciences, Pharmacology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3176250
ISBN:	9780542150111

Determinant of reinforcing efficacy of phenyltropanes: Onset of dopamine transporter occupancy.
Wee, Sunmee.

Determinant of reinforcing efficacy of phenyltropanes: Onset of dopamine transporter occupancy. - 106 p.

Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2533.

Thesis (Ph.D.)--The University of Mississippi Medical Center, 2005.

The purpose of this dissertation was to investigate a pharmacological determinant of reinforcing efficacy of stimulants. A slow onset of binding at the DAT is hypothesized to be associated with decreased reinforcing efficacy of DAT ligands. This hypothesis was evaluated with slow-onset cocaine analogs, WIN 35,428, RTI 31 and RTI 51. Reinforcing efficacy was assessed using a drug self-administration animal model. Onsets of DAT binding were measured using an in vivo binding assay. A correlation between reinforcing efficacy and onsets of DAT binding was made. Acquisition of self-administration of a slow-onset drug was also evaluated in drug-naive monkeys. Finally, monoamine pharmacodynamics of the drugs were compared using in vitro radioligand binding.

ISBN: 9780542150111Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Determinant of reinforcing efficacy of phenyltropanes: Onset of dopamine transporter occupancy.
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245 1 0 $a Determinant of reinforcing efficacy of phenyltropanes: Onset of dopamine transporter occupancy.
300 $a 106 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2533.
500 $a Adviser: William L. Woolverton.
502 $a Thesis (Ph.D.)--The University of Mississippi Medical Center, 2005.
520 $a The purpose of this dissertation was to investigate a pharmacological determinant of reinforcing efficacy of stimulants. A slow onset of binding at the DAT is hypothesized to be associated with decreased reinforcing efficacy of DAT ligands. This hypothesis was evaluated with slow-onset cocaine analogs, WIN 35,428, RTI 31 and RTI 51. Reinforcing efficacy was assessed using a drug self-administration animal model. Onsets of DAT binding were measured using an in vivo binding assay. A correlation between reinforcing efficacy and onsets of DAT binding was made. Acquisition of self-administration of a slow-onset drug was also evaluated in drug-naive monkeys. Finally, monoamine pharmacodynamics of the drugs were compared using in vitro radioligand binding.
520 $a When cocaine or a cocaine analog was made available to rhesus monkeys (n = 4 or 5) for self-administration under a progressive-ratio (PR) schedule with a one-hour time-out between injections, all the drugs functioned as positive reinforcers. The maximum number of injections was in the order of cocaine > WIN 35,428 > RTI 31 > RTI 51. In in vivo DAT binding in rats, the ED50 doses of cocaine, WIN 35,428, RTI 31 and RTI 51 were estimated to displace 25% of [3H]WIN 35,428 binding at the DAT, respectively, 5.8, 22.4, 30.8 and 44.1 min after the i.v. injection. That is, relative reinforcing efficacy was correlated with rate of DAT binding. In in vitro binding in monkey brain tissue, the cocaine analogs had higher affinity for monoamine transporter sites, but similar affinity ratios of 5-HTT/DAT, compared to cocaine. Further, RTI 31 was shown to function as a positive reinforcer in drug-naive rhesus monkeys under a fixed-ratio 1 (FR 1) schedule. Collectively, the data supports the hypothesis that a slow onset at the DAT is associated with reduced reinforcing efficacy of DAT ligands. The data under both the PR and FR schedules, however, suggest that a slow onset at the DAT influences reinforcing efficacy only to a limited extent. The similar affinity ratios of SERT/DAT in in vitro binding results argue against the role of serotonin in the difference of reinforcing efficacy of the compounds.
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790 1 0 $a Woolverton, William L., $e advisor
790 $a 0805
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