Academic journal article The Psychological Record

Separation, Motivation, and Depression: Neonatal Isolation Reduces Food-Rewarded Operant Responding in Rats

Academic journal article The Psychological Record

Separation, Motivation, and Depression: Neonatal Isolation Reduces Food-Rewarded Operant Responding in Rats

Article excerpt

A major symptom of depression is reduced motivation. Additionally, early separation stress has been associated with depression. Experiences of loss, such as death or separation, are correlated both with the early life histories of patients with depression (Gilmer & McKinney, 2003; Heim & Nemeroff, 2001; Luecken, 2000), and with the onset of primary depressive episodes (Kendler, Hettema, Butera, Gardner, & Prescott, 2003). Furthermore, disruptions in parent-child attachment are thought to lead to a variety of psychopathologies and vulnerabilities that include depression (Beebe & Lachmann, 2002; Fonagy, 2001; Schore, 1996). Given that both early stress and reduced motivation are associated with depression, we sought to investigate whether or not there exists a direct relation between early separation stress and impaired motivation.

The subjugation of rodents to early separation is considered to be a model of depression and has generated findings on the long-term effects of early stress on adult neurophysiology and behavior (Nestler et al., 2002). Manipulations include maternal separation (MS), in which the litter is separated from the dam for an extended period such as 24 hours; repeated maternal separation (RMS), in which a litter is separated from the dam for periods ranging from 1 to several hours over a span of days within the first several weeks of birth; and neonatal isolation (NI) or early deprivation (ED), in which individual pups are isolated from both the dam and littermates for a period of 1 to 6 hr over a span of days within the first several weeks of birth (see Pryce & Feldon, 2003, for review). Using these manipulations, studies have revealed a number of common features between the neurophysiology of these animals and human subjects with depression. For example, it is now well documented that both humans with depression and rodents affected by early separation show dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (for human reviews, see Erickson, Drevets, & Schulkin, 2003; Gutman & Nemeroff, 2003; Heim & Nemeroff, 2001; for rodent reviews, see Cirulli, Berry, & Alleva, 2003; Levine, 2001; Pryce & Feldon, 2003).

Early life stress has also been correlated with changes in dopamine (DA) neuronal systems, key substrates for reward and motivation. For example, early separation experience leads to increased striatal levels of DA and decreased prefrontal turnover of DA (Matthews, Dalley, Matthews, Tsai, & Robbins, 2001), reduced tyrosine hydroxylase-immunoreactive fibers in some regions of frontal cortex (Braun, Lange, Metzger, & Poeggel, 2000) and increased tyrosine hydroxylase-immunoreactive fibers in others (Poeggel, Nowicki, & Braun, 2003). Given these changes, it might be expected that early separation would lead to changes in reward-related behavior.

Indeed, early separation paradigms have been used to investigate the effects on reward-related behavior. Most of these studies have incorporated drug rewards, pharmacological manipulations, or both (e.g., Kehoe, Shoemaker, Triano, Callahan, & Rappolt, 1998; Kosten, Miserendino, & Kehoe, 2000; Matthews, Hall, Wilkinson, & Robbins, 1996; Matthews, Robbins, Everitt, & Caine, 1999; Zhang, Sanchez, Kehoe, & Kosten, 2005). However, given that many humans develop depression without any experience with exogenous chemicals, it is important to understand the effects of early separation on motivation in relation to natural rewards. Only a few studies to date have done so.

No differences have been found in basic consummatory behavior between early separated animals and comparison groups (Iwasaki, Inoue, Kiriike, & Hikiji, 2000; Matthews, Hall, et al., 1996). However, differences have been found in conditioned responding for natural reward in maternally separated rats. RMS resulted in reduced anticipatory locomotion in response to food (Matthews, Hall, et al. …

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