Comunicación

EFFECTS OF CRF1R ANTAGONISTS IN RELAPSE AFTER PHYSICAL STRESS

Autores:

ALBERTO CANOVAS CABANES1, M. Pilar Almela Rojo2, Javier Navarro Zaragoza2, M. Luisa Laorden Carrasco2

Afiliaciones:

(1) doctorando farmacología, 30003, España (Región de Murcia)
(2) FARMACOLOGÍA CELULAR Y MOLECULAR, IMIB-Arrixaca, España

Comunicación:

Antecedentes:

It has been observed an increase in opioid drug administration in recent years, which sometimes involves drug addiction. Addiction to substances of abuse is a chronic neurological disorder characterized by drug-seeking, compulsive consumption, and frequent relapses during periods of abstinence. Many studies have proposed that stress has a key role in the development of drug addiction with connections between noradrenergic system and brain stress system (García-Carmona JA et al, 2013), but also in relapse. The aim of this work was to analyze the influence of a physical stressor (Social Defeat) in relapse associated with morphine in mice pretreated with CP-154,526, a selective CRF1 receptor (CRF1R) antagonist.

Métodos:

Sixty-four male mice (C57BL/6j) were divided into eight groups according to whether they were treated with morphine or saline, received stressful stimulus (Social Defeat) or were controls (social defeat control) and depending on whether they were injected with drug (CP-154,526) or vehicle. Those mice in the morphine group were treated with increasing doses of morphine (10, 30, 50 and 60 mg/kg) and a dose of naloxone (1 mg/kg) on the fourth day in a manner that induce drug-related conditioned place aversion (CPA). After 7-10 sessions, once the aversion was extinguished in all mice, CP-154,526 (30 mg/kg i.p.) was administered and, after 30 minutes, the target group received the stressor. As for the other groups, some received saline instead of morphine or saline instead of the drug.

Resultados:

Our results showed a statistically significant decrease in the time spent during the post-test by mice treated with morphine in the compartment where naloxone was administered, which assures the state of aversion. Once aversion was extinguished, Social Defeat induced a relapse in the aversive behavior (p<0.05). Besides, administration of CP-154,526 in animals receiving the stressor significantly increased the time that the animals stayed in the aversive compartment, compared to the stressed group that did receive the CRF1R antagonist (p<0.05) (Figure 1).

Conclusiones:

Our results show that administration of CP-154,526 to animals that received a stressful stimulus does not trigger a relapse in the previous aversive behavior. Therefore, these results suggest that CRF1R antagonists would be good candidates for the treatment of addicted subjects in the prevention of relapses in the consumption of substances of abuse.


Image 1

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Campus de Ciencias de la Salud
Carretera Buenavista s/n, 30120 El Palmar
Murcia, España

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