The Role of Trace Amine Associated Receptor‐1 (TAAR‐1) on the Modulation of Circadian Rhythms in Mice
Authors: Zejnilovic Nadin , Clough Shannon J. , Glatfelter Grant C. , Phillips Tamara J. , Dubocovich Margarita L. 
Published: June 2021

Methamphetamine (MA) can alter circadian rhythms by increasing the period length or Tau (Olsen et al., 2013). The Trace Amine Associated Receptor‐1 (TAAR‐1) is associated with alterations in the sensitivity to MA (Harkness et al., 2015). From the F2 cross of C57BL/6J mice, which have a functional TAAR‐1 and exhibit low levels of MA consumption, and DBA/2J mice, which lack a functional TAAR‐1 and have high levels of MA consumption, our collaborators selectively bred MA Low Drinking (MALDR) and MA High Drinking (MAHDR) mice (Harkness et al., 2015). In a prior study, MALDR mice exhibited increased sensitivity to the period lengthening effects of MA provided via drinking water compared to MAHDR mice (Olsen et al., 2013). The goal of the present study was to determine whether there are distinct circadian phenotypes in mice with a non‐functional TAAR‐1 (MAHDR) compared to mice with a functional TAAR‐1 (MALDR), and to examine the impact of MA. The Home Cage Scan was initially used to distinguish any basal difference in activity, ingestive, exploratory/anxiety‐like, and sleep behaviors between the two genotypes. Mice were then subjected to a 6‐h phase advance of the dark onset to assess re‐entrainment. This was followed by a 6‐day period of saline injections, with a 5‐day break, followed by a 6‐day period of 1.2 mg/kg MA ip injections. The light cycle was then changed to constant dark, in order to allow for the assessment of endogenous rhythms and examine the ability of the two genotypes to phase shift in response to a light‐pulse (300lx for 15 minutes). Overall, no significant differences were found between the MALDR and MAHDR mice in any of the home cage behaviors examined. Additionally, no significant differences were found between genotypes in terms of the days (MALDR: 8.3±0.6d, n=11; MAHDR: 8.0±0.6d, n=13) and hours/day to re‐entrainment to a 6‐h phase advance. The two genotypes also displayed a similar level of change in percent daily activity for both saline and MA anticipatory (Saline: MALDR 0.003±0.003, n=9; MAHDR 0.02±0.018, n=14; MA: MALDR 0.16±0.16, n=9; MAHDR 0.13±0.12, n=14) and induced activity (Saline: MALDR 9.33±3.97, n=9; MAHDR 2.71±1.43, n=14; MA: MALDR 8.72±2.35, n=9; MAHDR 12.09±2.06, n=14). There were also no differences observed in the ability of the two genotypes to phase shift in response to a light‐pulse (MALDR: 1.77±0.17h, n=8; MAHDR: 1.77±0.22h, n=14). We suggest that the variation in MA sensitivity observed in previous studies may be dependent on route of MA administration (oral in drinking water vs. ip injection). We conclude TAAR‐1 and/or selective breeding for MA intake does not play a role in the modulation of the circadian parameters we tested.Support or Funding InformationSupported by UB Jacobs School of Medicine and Biomedical Sciences funds to MLD, and by NIH NIDA P50 DA018165, U01 DA041579, and VA Merit Review grant I01BX002106 to TJP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.