Increased 5-HT2C receptor responsiveness occurs on rearing rats in social isolation

Abstract

To investigate whether isolation rearing alters 5-hydroxytryptamine2C (5-HT2C) receptors, the effect of the serotonin agonist m-chlorophenylpiperazine (mCPP) was examined on elevated plus-maze behaviour, plasma corticosterone and brain 5-HT2C receptor protein levels in rats. There was no distinction between behaviour or corticosterone levels in drug-free isolates or socially housed rats exposed to the elevated plus-maze. The anxiogenic response to mCPP (decrease in open arm entry and time and an increase in stretch attend postures) on the elevated plus-maze was greater in isolation than in socially reared controls without any concomitant difference in the hypolocomotor effect of mCPP in the two groups. mCPP produced a greater elevation in plasma corticosterone in isolates than in group-housed controls. Hippocampal 5-HT2C receptor protein-like immunoreactive levels were significantly lower following mCPP than saline only in rats reared in isolation. These results indicate that increased 5-HT2C receptor responsiveness accompanies isolation-rearing and may contribute to the enhanced response to stress and the increased neophobia seen in this animal model of trait anxiety/depression. In isolation reared rats, rapid down-regulation of supersensitive 5-HT2C receptors may occur in the hippocampus following 5-HT agonist challenge.

Dysregulation of Diurnal Rhythms of Serotonin 5-HT2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

“…Furthermore, animals reared in isolation have increased sensitivity to 5-HT 2C agonists (Fone et al, 1996), confirming in another model of depression the importance of 5-HT 2C receptor sensitivity. Patients with depression exhibit abnormal circadian rhythms of plasma cortisol, with a prolonged peak and early timing of the nadir, although a transient (or elevated) nadir usually occurs (Linkowski et al, 1987).…”

Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats

“…Animals exposed to prior stress exhibit an enhanced, reduced or equivalent hypothalamic-pituitary-adrenal response to a subsequent acute stressor (5-7). Social isolation produced by individual housing affects brain monoamine and adrenal gland functions in experimental animals (8)(9)(10)(11). Social isolation and acute environmental changes are risk factors in human depression, and represent a lack of the social stimuli necessary to modulate adaptive responses to new situations (12).…”

Interaction of nitric oxide and serotonin in aggressive behavior

“…Manipulations of 5-HT receptors with various agonists and antagonists have revealed that social isolation in rodents differentially affects 5-HT receptor subtypes (Wright et al, 1991;White et al, 1991;Sanchez et al, 1993;Fone et al, 1996). Binding studies show transient down-regulation of presynaptic 5-HT 1A receptors in the midbrain of mice isolated for 3-6 weeks (Rilke et al, 1998).…”