Intracranial self-stimulation and concomitant behaviors following systemic methamphetamine administration in Hnrnph1 mutant mice

Abstract

Rationale. Addiction to methamphetamine (MA) is a public health issue in the United States. While psychostimulant use disorders are heritable, their genetic basis remains poorly understood. We previously identified heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1; H1) as a quantitative trait gene underlying sensitivity to MA-induced locomotor activity. Mice heterozygous for a frameshift deletion in the first coding exon of H1 (H1 +/-) showed reduced MA-induced locomotor activity, dopamine release, and dose-dependent differences in MA conditioned place preference. However, the effects of H1 +/on innate and MA-modulated reward sensitivity are not known.Objectives. We examined innate reward sensitivity and modulation by MA in H1 +/mice via intracranial selfstimulation (ICSS).Methods. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle to assess shifts in reward sensitivity following acute, ascending doses of MA (0.5-4.0 mg/kg, i.p.) at 10 min or 2 h post-MA. We also assessed video-recorded behaviors during ICSS testing sessions.Results. Ten min post-MA, H1 +/mice displayed reduced maximum response rates, H1 +/females had lower M50 values than wild-type females, and H1 +/influenced ICSS responding relative to maximum control rates (MCR). Two h post-MA, higher response rates were observed in females, irrespective of genotype. There was a dose-dependent reduction in distance to the response wheel 10 min post-MA and reduced immobility time in the perimeter corners both 10 min and 2 h post-MA.Conclusions. H1 +/mice displayed altered MA-induced reward modulation in a time-, sex-, and dose-dependent manner. This expands the set of MA-induced phenotypes observed in H1 +/mice.

Cacna2d2 is an hnRNP H target of the striatal mRNA targetome and regulates methamphetamine behavior

“…Accumulating evidence from our lab indicates a role for hnRNP H in methamphetamine addiction liability (Ruan et al, 2020a;Borrelli et al, 2021). Defining the set of RNA targets in brain tissue that are differentially regulated by hnRNP H in Hnrnph1 mutants in response to methamphetamine could inform key mechanisms underlying decreased dopamine release and behavior.…”

Validación de la teoría del aprendizaje de Juan Enrique Azcoaga con ratones CD-1 mediante observación directa: Aprendizaje fisiológico

“…La motivación, es uno de los dispositivos básicos, conocido como "el estado de excitabilidad óptimo para iniciar un condicionamiento, como una de las condiciones del sistema nervioso central que hacen posible comenzar un proceso de aprendizaje" [8]. Así mismo se considera emocional y no racional.…”

“…La Autoestimulación Eléctrica Intracraneal (AEIC) es un tratamiento que ha ayudado a demostrar y facilitar la consolidación de la memoria de los vertebrados e invertebrados que se encuentran en los laboratorios, para la respectiva experimentación e investigación, de igual forma el condicionamiento clásico aversivo, apetitivo, condicionamiento operante y el pre-condicionamiento sensorial facilitan el aprendizaje y memoria, siendo así la AEIC considerado un método empírico útil para analizar los procesos cognitivos [8,16,22,29].…”