Efecto de la cocaína sobre la inhibición por prepulso de la respuesta de sobresalto

Abstract

Introducción. La inhibición por prepulso (IPP) de la respuesta de sobresalto es una medida de sincronización sensitivomotora basada en la respuesta del reflejo de sobresalto. Un déficit en la IPP se ha observado en pacientes psiquiátricos, especialmente con esquizofrenia, así como en sujetos vulnerables a desarrollarla. Asimismo, los consumidores de cocaína presentan un alto índice de patologías psiquiátricas como la esquizofrenia. Objetivo. Conocer las alteraciones que el consumo de cocaína puede producir en la IPP. Desarrollo. Se realiza una revisión exhaustiva de los estudios, tanto clínicos como con modelos animales, que hayan evaluado la IPP tras el consumo o la administración de cocaína. Se sugieren bases neurales y mecanismos de acción subyacentes para explicar los resultados. Conclusiones. La cocaína altera la IPP a través de su acción sobre el sistema dopaminérgico. La administración aguda de cocaína disminuye la IPP al aumentar la dopamina, mientras que con el consumo crónico, dependiendo del tiempo de abstinencia, la IPP puede restablecerse. Sin embargo, los efectos de la cocaína sobre la IPP parecen depender de los niveles basales de la IPP que muestre el individuo. Así, dado que un déficit en la IPP se ha relacionado con una mayor vulnerabilidad a desarrollar patologías mentales como la esquizofrenia, los niveles de la IPP en los sujetos podrían considerarse como un biomarcador de vulnerabilidad psiquiátrica. Por ello, conocer mejor el efecto que drogas como la cocaína ejercen sobre la IPP puede ayudar a comprender el desarrollo de la patología dual. Palabras clave. Cocaína. Dopamina. Inhibición por prepulso. Trastornos psiquiátricos.

Prepulse Inhibition of the Startle Reflex as a Predictor of Vulnerability to Develop Locomotor Sensitization to Cocaine

“…Amphetamine decreases PPI in a strain of rats with a relatively low COMT gene expression in the NAc, while it increases PPI in another strain of rats with relatively high COMT gene expression in the NAc (Talledo et al, 2009). In light of this evidence, DA availability in the NAc seems to be critical in determining the level of PPI observed; i.e., a higher DA level will induce a PPI deficit, while a lower DA level will increase PPI (Arenas et al, 2017). The role of DA in determining PPI levels has been bolstered since activation of midbrain cholinergic neurons has been shown not to mediate PPI levels (Azzopardi et al, 2018).…”

“…The role of DA in determining PPI levels has been bolstered since activation of midbrain cholinergic neurons has been shown not to mediate PPI levels (Azzopardi et al, 2018). One of the main brain nuclei that modulate PPI is the pedunculopontine tegmentum (PPTg; Arenas et al, 2017), which is one of the major cholinergic centers of the brain (Gut and Winn, 2016). However, it has recently been demonstrated that cholinergic PPTg neurons do not mediate PPI, in contrast to a longstanding hypothesis maintaining that they do (Azzopardi et al, 2018).…”

“…Recently, given that neural structures regulating PPI and drug addiction have been shown to coincide (Volkow and Morales, 2015;Arenas et al, 2017), we have begun to evaluate the predictive ability of PPI in order to identify animals that are more sensitive to the effects of cocaine. In a previous study (Arenas et al, 2018), we showed that the baseline PPI level of mice predicts their sensitivity to the conditioned reinforcing effects of cocaine in the conditioned place preference (CPP) paradigm.…”

Prepulse Inhibition in Cocaine Addiction and Dual Pathologies

“…PPI is a good neurobiological marker between different species because it is hereditary and does not become habituated or eliminated over repeated tests [ 9 , 17 , 18 , 19 , 20 ]. Moreover, PPI is reduced in patients with schizophrenia, making it a good endophenotype for this pathology [ 21 , 22 , 23 , 24 , 25 , 26 ], and lower PPI is also associated with antisocial characteristics [ 27 , 28 ]; a recent study used PPI to discriminate between patients with APD alone or APD with psychopathy [ 29 ]. We also previously showed that patients with CRD + SCZ or CRD + APD presented PPI deficits compared to patients with CRD without a DP [ 30 ].…”

“…In mice, baseline PPI also correlated with sensitivity to the reinforcing effects of cocaine in the conditioned place preference paradigm; animals with low PPI had higher striatal DA D2 receptor expression and required higher doses of cocaine (12 mg/kg) to acquire a conditioned preference than those with higher PPI [ 9 ]. Thus, DA availability in the NAc appears to be critical in determining the PPI; higher DA levels induce a PPI deficit, while lower DA levels increase PPI [ 21 , 35 ]. Together, these data suggest that patients with lower PPI levels present dopaminergic system alterations that increase their vulnerability to CRD.…”