Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome.
Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition 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 determined by measuring dopamine and serotonin as well as their major metabolites in a "psychosis circuit" that includes mainly the hippocampus and selected 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 demonstrate that rearing rats in isolation (i) produces a syndrome of generalized locomotor hyperactivity; (ii) increases the startle response; (iii) impairs prepulse inhibition; (iv) tends to increase food hoarding behavior; (v) increases basal dopamine turnover in the amygdaloid complex; (vi) decreases basal dopamine turnover in the infralimbic part of the medial prefrontal cortex; and (vii) decreases basal turnover of serotonin in the nucleus accumbens. In the entorhinal cortex, dopamine neurotransmission seemed to be more sensitive to the caging conditions since a decreased basal turnover of dopamine was observed in grid-reared animals. Plasma corticosterone levels were also increased in grid-reared animals compared with rats reared in sawdust cages. Finally, isolates reared on grids showed a significant positive correlation between plasma corticosterone levels and dopamine in the left nucleus accumbens.Altogether, these results support the contention that there is a link between 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 form of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine activity in the left nucleus accumbens. Finally, a significant and selective decrease in the basal turnover of serotonin in the nucleus accumbens of isolated rats may be linked to the isolation-induced locomotor hyperactivity.
Heidbreder
C A
CA
SmithKline Beecham Pharmaceuticals, Department of Neuroscience, New Frontiers Science Park (North), Building H25, Room 104A, Essex CM19 5AW, Harlow, UK. Christian_A_Heidbreder@sbphrd.com
Weiss
I C
IC
Domeney
A M
AM
Pryce
C
C
Homberg
J
J
Hedou
G
G
Feldon
J
J
Moran
M C
MC
Nelson
P
P
D000161:Acoustic Stimulation; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D004703:Endocrine System / Q000378:metabolism*; D005247:Feeding Behavior; D007839:Functional Laterality; D008297:Male; D017551:Microdialysis; D009043:Motor Activity; D051381:Rats; D013216:Reflex, Startle; D012701:Serotonin / Q000378:metabolism; D012934:Social Isolation; D013577:Syndrome
D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D004298:Dopamine; D003345:Corticosterone