| First Author | Borrelli KN | Year | 2021 |
| Journal | Psychopharmacology (Berl) | Volume | 238 |
| Issue | 7 | Pages | 2031-2041 |
| PubMed ID | 33758972 | Mgi Jnum | J:344648 |
| Mgi Id | MGI:6881648 | Doi | 10.1007/s00213-021-05829-4 |
| Citation | Borrelli KN, et al. (2021) Intracranial self-stimulation and concomitant behaviors following systemic methamphetamine administration in Hnrnph1 mutant mice. Psychopharmacology (Berl) 238(7):2031-2041 |
| abstractText | RATIONALE: Methamphetamine (MA) addiction is a major public health issue in the USA, with a poorly understood genetic component. We previously identified heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1; H1) as a quantitative trait gene underlying sensitivity to MA-induced behavioral sensitivity. Mice heterozygous for a frameshift deletion in the first coding exon of H1 (H1(+/-)) showed reduced MA phenotypes including oral self-administration, 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 facilitation by MA in H1(+/-) mice via intracranial self-stimulation (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.) using a within-subjects design. We also assessed video-recorded behaviors during ICSS testing sessions. RESULTS: H1(+/-) mice displayed reduced normalized maximum response rates in response to MA. H1(+/-) females had lower normalized M50 values compared to wild-type females, suggesting enhanced reward facilitation by MA. Finally, regardless of genotype, there was a dose-dependent reduction in distance to the response wheel following MA administration, providing an additional measure of MA-induced reward-driven behavior. CONCLUSIONS: H1(+/-) mice displayed a complex ICSS phenotype following MA, displaying indications of both blunted reward magnitude (lower normalized maximum response rates) and enhanced reward sensitivity specific to H1(+/-) females (lower normalized M50 values). |
