Mother-infant separation leads to hypoactive behavior in adolescent Holtzman rats

Abstract

This is the first study of the effects of mother-infant separation (MS) on adolescent behavior of Holtzman (HO) rats. Different rat strains, such as Harlan Sprague-Dawley and HO, share a common origin. However, MS may lead to hypoactive behavioral effects in HO rats because of their greater susceptibility to show depressive-like responses to stress. Sixty HO pups were divided into three groups at postnatal day 2 (P2). For 10 days, the MS group was separated 6h daily and the early handled (EH) group 15 min daily. A standard facility reared (SFR) group was not separated. Animals were tested for novel open-field activity (P28), defensive withdrawal in a light-dark (LD) apparatus (P29) and familiar open-field (P30). Behavioral measures were classified into general activity (ambulatory and short movement time), orienting (rearing time) and risk-taking (velocity and exposed zone time). MS rats displayed reductions in general activity and risk-taking, and increases in orienting time. In contrast, EH favored risk-taking behavior, which may be consistent with previous findings implicating early handling as beneficial in coping with stress. Sex differences in these behaviors were limited. This study suggests a genetic predisposition in HO rats for predominantly hypoactive/anxiety-like behaviors when exposed to an early life stressor.

Fig. 1. Group effects on behavioral measures as a function of time (min) in the novel open-field test (OFT), light-dark test, and familiar OFT for maternally separated (MS), early handled (EH), and standard facility reared (SFR) groups

A: Ambulatory time (mean plus standard error). B: Short movement time (mean plus standard error). The MS group showed less ambulatory (p = 0.035) and short movement activity (p = 0.017), particularly in the first two sessions. C: The MS group showed less exposed-zone time (mean plus standard error) on P29 (p = 0.013); i.e., remained in the safe dark compartment. The EH group showed the opposite effect during this test. D: The MS group showed greater rearing time (mean plus standard error), but only significantly (p = 0.001) on the familiar OFT.

Fig. 2. Sex differences in behavior

A: Short movement time (mean plus standard error) as a function of time (min) in the novel open-field test. Males showed more short movement activity than females (p = 0.028). Males also showed more impulsivity (B: ambulatory velocity) (p = 0.017) and risk-taking (C: exposed zone-time) (p = 0.002) than females in the novel open field.