Social Isolation in the Rat Produces Developmentally Specific Deficits in Prepulse Inhibition of the Acoustic Startle Response Without Disrupting Latent Inhibition

Abstract

A series of experiments examined the effects of 8 weeks of social isolation on spontaneous locomotor activity, prepulse inhibition (PPl) of the acoustic startle response, latent inhibition (LI) in a conditioned suppression paradigm, and basal and d-amphetamine stimulated dopamine (DA) release in the ventral striatum, as measured by in vivo microdialysis. Both isolation-reared animals (those isolated from the weaning age) and isolation-housed animals (those isolated as adults) were hyperactive when placed in a novel environment. Social isolation also led to deficits in PPI of the acoustic startle KEY WORDS: Social isolation; Locomotor activity; Prepulse inhibition; Latent inhibition; Dopamine; Ventral striatumVariations in early social experience have been shown to have profound effects on the adult behavior, brain morphology, and neurochemistry of a variety of spe cies (Sachser 1986;Lewis et al. 1990;Martin et al. 1991;Jones et al. 1992). For example, rearing rats in social iso lation from the weaning age produces behavioral ab normalities that include increases in spontaneous and response that were specific to isolation-reared animals. Isolation rearing was without effect on the expression of LI but did lead to an enhanced response to systemic d-amphetamine in terms of striatal DA release. The data are discussed with respect to the involvement of ventral striatal DA mechanisms in the expression of PPI and LI, differences in the impact of social isolation in young and adult animals, and the utility of social isolation model as a nonlesion, nonpharmacologic means of perturbing ventral striatal DA function.

Impulsive choice and environmental enrichment: Effects of d-amphetamine and methylphenidate

“…Each of these models has both strengths and limitations; for example, SHR rats exhibit many of the behavioral characteristics of ADHD, but hypertension is a confounding factor in this model [79]. Isolation rearing may be a useful model because, in addition to the increased impulsivity noted in IC rats in the current study, IC rats are also hyperactive [13,26,47,80] and show attentional deficits [5,16,19,30,33,88,92] compared to EC rats. Further, in the current study, amphetamine decreased preservative non-reinforced responding in IC rats.…”

Norepinephrine Transporter Blockade can Normalize the Prepulse Inhibition Deficits Found in Dopamine Transporter Knockout Mice

“…Obviously, attentional and cognitive components of ADHD symptomatology may not be reflected by this model. It remains to be seen if PPI deficits induced by psychostimulants or dopaminergic overactivity (Wilkinson et al, 1994;Barr et al, 2004) reflect the sort of attentional deficits observed in ADHD. Nonetheless, it is interesting to note that selective serotonin reuptake inhibitors (SSRIs) are reported to be ineffective in ADHD (Findling, 1996), even though fluoxetine appears to reduce hyperactivity in DAT KO mice (Gainetdinov et al, 1999).…”

Isolation rearing in the rat disrupts the hippocampal response to stress

“…For example, isolation enhances mesolimbic function (Jones et al, 1992), resulting in increased dopamine and 5-HT function in the striatum (Jones et al, 1992;Wilkinson et al, 1994;Robbins et al, 1996;Fulford and Marsden, 1998;Hall et al, 1998), but reduces hippocampal, serotonergic and noradrenergic responsiveness (Wright et al, 1990(Wright et al, , 1991Bickerdike et al, 1993). Changes in hippocampal formation following isolation rearing may trigger compensatory changes within systems that depend on normal hippocampal input using glutamatergic transmission.…”