Sex, but not repeated maternal separation during the first postnatal week, influences novel object exploration and amphetamine sensitivity

Abstract

Sensation seeking and early life stress are both risk factors for developing substance use disorders. Neural adaptations resulting from early life stress may mediate individual differences in novelty responsiveness, and, in turn, contribute to drug abuse vulnerability. Animal models also demonstrate associations between novelty responsiveness or early life stress and increased sensitivity to psychostimulants. We investigated whether repeated maternal separation affects responses to novelty during adolescence and to amphetamine during adulthood, and whether maternal separation alters the relationship between these behavioral variables. Rat pups underwent separation (180 min/day) or control procedures (15 min/day) on postnatal days (PND) 2-8. Novel object exploration and amphetamine response were tested at PND 38 and 60, respectively. Adolescent males were less active in a novel environment and approached novel objects more frequently than females, but adult females showed greater amphetamine-induced locomotion. Maternal separation did not affect novelty responsiveness or amphetamine sensitivity. Locomotor activity in an inescapable, novel environment during adolescence predicted amphetamine-induced locomotor activity during adulthood in maternally separated rats, but not in controls. The results of this study suggest that adolescent responses to novelty may be particularly predictive of future substance abuse among survivors of early life trauma. Furthermore, sex differences in novelty and amphetamine responsiveness may complicate the relationship between these behavioral variables.

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring

“…All females, regardless of maternal opioid history showed increased locomotor activity compared with males in response to a novel environment. This has been shown repeatedly and recapitulates what is known in the literature (Hensleigh et al, 2011; Spivey et al, 2009; Wooters et al, 2006). CPP is posited to measure cue-elicited conditioning that can motivate drug-taking behavior (Bardo et al, 1995; Robbins and Ehrman, 1992).…”

Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats

“…Similarly, Marin and Planeta (2004) observed increased sensitivity to the locomotor activating effects to cocaine in adolescent MS rats, relative to non-handled controls. However, other studies have found no difference between MS and control rats in behavioral responses to d-amphetamine (Hensleigh et al 2011; Marmendal et al 2004; Muhhamad and Kolb 2011). These divergent findings are likely due to methodological differences in the MS procedure, such as duration, frequency and developmental timing of separation, as well as the age at which behavioral testing occurred.…”

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…Most studies show an increase (Zimmerberg and Shartrand, 1992;Kehoe et al, 1996Kehoe et al, , 1998Pryce et al, 2001;Brake et al, 2004;Marin and Planeta, 2004;Kikusui et al, 2005) or no effect (Lehmann et al, 1998;Li et al, 2003;Marmendal et al, 2004;Kosten et al, 2005a,c;Hensleigh et al, 2011) compared with stimulant effects in controls, whereas others show a decrease (Matthews et al, 1996a;Moffett et al, 2006). Factors that likely account for these differences are drug history before acute stimulant administration, doses of stimulant tested, and sex.…”