Baseline prepulse inhibition of the startle reflex predicts the sensitivity to the conditioned rewarding effects of cocaine in male and female mice

Abstract

Low-PPI mice presented a lower sensitivity to the conditioned rewarding effects of cocaine, but once they were conditioned with a higher dose, they displayed a stronger, perseverant conditioned preference. The predictive capacity of PPI to detect the more vulnerable mice to the conditioned effects of cocaine is discussed.

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

“…Given that our objective was to demonstrate the predictive capacity of the PPI paradigm to detect vulnerability to developing motor sensitization regardless of the procedure used, we decided to use both methods. Additionally, we considered it necessary to evaluate the motor effect of an acute dose of cocaine (10 mg/kg), as we expected that Low-PPI mice would display lower sensibility to the effects of cocaine than High-PPI mice, in accordance with the results in Arenas et al (2018). Although mice received a single dose of cocaine in the sensitization procedure, those in the control group had previously received a regime of saline injections, which could have created a stressful context that increased the sensibility of mice to the effects of cocaine (Ferrer-Pérez et al, 2018.…”

“…After an adaptation period of 5 days, all the mice about to be included in an experiment performed the pre-pulse inhibition test (PPI), on PND 46-65. The procedure, similar to that used in previous studies (Arenas et al, 2018), was carried out in two phases (acclimation and test) over 2 days. On the first day, mice were placed in the animal holder for 5 min with a constant 65-dB white noise as background noise, but without startle stimuli.…”

“…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. Mice with a high PPI-both males and females-acquired CPP with a subthreshold dose of cocaine (1 mg/kg) and with an effective dose (6 mg/kg), while animals with a low PPI did not present conditioned preference with either of these two doses.…”

“…These behavioral differences could have been related to differences in the levels of D1 and D2 dopamine receptors in the striatum of these animals. For instance, mice with a low PPI, especially females, presented higher levels of D2 receptor expression (Arenas et al, 2018).…”

“…This neuroplasticity induced by cocaine use is observed specifically in the dopaminergic system, from the ventral tegmental area to the nucleus accumbens (NAc), which is also a central circuit for the regulation of PPI (Doherty et al, 2008;Rohleder et al, 2016). Moreover, the behavioral effects of cocaine are mediated by D1 and D2 receptors, which have also been associated with baseline PPI levels (Doherty et al, 2008;Arenas et al, 2018). If a PPI deficit indicates alterations in the mesolimbic dopaminergic system , it is possible that a subject with low PPI is more vulnerable to the cerebral changes induced by cocaine use.…”