Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome

Rearing rats in isolation has been shown to be a relevant paradigm for stud ying early life stress and understanding the genesis of depression and rela ted affective disorders. Recent studies from our laboratory point to the re levance of studying the social isolation syndrome as a function of home cag ing conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibitio n of the acoustic startle, food hoarding and spontaneous locomotor activity . In addition, ex vivo neurochemical changes in the brains of isolated and grouped rats reared either in sawdust-lined or in grid-floor cages were det ermined by measuring dopamine and serotonin as well as their major metaboli tes in a "psychosis circuit" that includes mainly the hippocampus and selec ted hippocampal efferent pathways projecting towards the anterior cingulate and infralimbic cortices, nucleus accumbens, dorsolateral caudate nucleus, amygdala and entorhinal cortex. The results of the present study demonstra te that rearing rats in isolation (i) produces a syndrome of generalized lo comotor hyperactivity; (ii) increases the startle response; (iii) impairs p repulse inhibition; (iv) tends to increase food hoarding behavior; (v) incr eases basal dopamine turnover in the amygdaloid complex: (vi) decreases bas al dopamine turnover in the infralimbic part of the medial prefrontal corte x; and (vii) decreases basal turnover of serotonin in the nucleus accumbens . In the entorhinal cortex, dopamine neurotransmission seemed to be more se nsitive to the caging conditions since a decreased basal turnover of dopami ne was observed in grid-reared animals. Plasma corticosterone levels were a lso increased in grid-reared animals compared with rats reared in sawdust c ages. Finally, isolates reared on grids showed a significant positive corre lation between plasma corticosterone levels and dopamine in the left nucleu s accumbens. Altogether, these results support the contention that there is a link betwe en social isolation, attention deficit, spontaneous locomotor hyperactivity and reduced dopamine turnover in the medial prefrontal cortex. Furthermore , our data demonstrate that rearing rats in grid-floor cages represents a f orm of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine act ivity in the left nucleus accumbens. Finally, a significant and selective d ecrease in the basal turnover of serotonin in the nucleus accumbens of isol ated rats may be linked to the isolation-induced locomotor hyperactivity. ( C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.