Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors.
Pharmacol Biochem Behav
; 175: 123-129, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30308214
ABSTRACT
AIMS:
The dopamine D3 receptor (D3R) is a pharmacotherapeutic target for drug dependence. We have successfully imaged human D3Rs using radiolabeled LS-3-134, an arylamide phenylpiperazine with moderate selectivity for the D3R over D2R and low efficacy at the D2 and D3R. In this study, we screened for effects of LS-3-134 as a potential anti-cocaine therapeutic.METHODS:
Male rats were pretreated with LS-3-134 (0, 1.0, 3.2, or 5.6â¯mg/kg, IP) 15â¯min prior to tests for its effects on spontaneous and cocaine-induced locomotion. We next investigated the effects of LS-3-134 (0, 1.0, 3.2, 5.6, or 10.0â¯mg/kg, IP) on operant responding on a multiple variable-interval (VI) 60-second schedule with alternating cocaine (0.375â¯mg/kg, IV) and sucrose (45â¯mg) reinforcer components. Additionally, we tested LS-3-134 (5.6â¯mg/kg, IP) effects on a progressive ratio (PR) schedule of cocaine reinforcement, on extinction of cocaine-seeking behavior, and on reinstatement of extinguished cocaine-seeking behavior by cocaine-associated light/tone cues.RESULTS:
LS-3-134 did not alter spontaneous locomotion, but reduced cocaine-induced locomotion, break points on the high-effort progressive ratio schedule of reinforcement, and responding during extinction and cue reinstatement. In contrast, LS-3-134 did not alter cocaine or sucrose reinforcement on the low-effort multiple VI 60-second schedule.CONCLUSIONS:
The effects of LS-3-134 are similar to other dopamine D3 low efficacy partial agonists and antagonists in attenuating cocaine intake under high effort schedules of reinforcement and in attenuating cocaine-seeking behavior elicited by cocaine-associated cues. These findings are consistent with the anti-craving profile of other dopamine D3 drugs.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperazinas
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Benzamidas
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Agonistas de Dopamina
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Receptores de Dopamina D3
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharmacol Biochem Behav
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos