Differential effects of stress on presynaptic and postsynaptic 5-hydroxytryptamine-1A receptors in the rat brain: an in vitro electrophysiological study.

Extracellular and intracellular recording techniques were used to assess possible changes in the functional properties of 5-hydroxytryptamine-1A receptors in brain slices prepared from rats subjected to different stress paradigms. Whereas a 30-min restraint stress did not alter the inhibitory influence of ipsapirone on the firing of serotoninergic neurons in the dorsal raphe nucleus, the same session followed by a 24-h isolation produced a significant decrease in the potency of the 5-hydroxytryptamine-1A agonist to inhibit the electrical activity of these cells. Similarly, exposure of the animals to novel uncontrolled environmental conditions for 16 h significantly reduced the potency of ipsapirone to decrease the firing rate of serotoninergic neurons in brain stem slices. The effects of the latter two stressful paradigms were observed in slices from intact rats, but not in those from adrenalectomized animals. Intracellular recording showed that exposure of the animals to novel uncontrolled environmental conditions markedly reduced the potency of 5-carboxamidotryptamine to hyperpolarize serotoninergic neurons in the dorsal raphe nucleus and to decrease the input resistance of their plasma membrane. In contrast, the same stressful paradigm exerted no significant influence on the membrane effects of this 5-hydroxytryptamine-1A agonist on pyramidal cells in the CA1 hippocampal area. These data show that, like the direct application of corticosterone on to brain slices [Laaris N. et al. (1995) Neuropharmacology 34, 1201-1210], the stress-induced in vivo elevation of serum levels of endogenous corticosterone is associated with desensitization of somatodendritic 5-hydroxytryptamine-1A receptors in the dorsal raphe nucleus. The differential changes in 5-hydroxytryptamine-1A receptor sensitivity due to stress in the latter area versus the hippocampus further support the idea that somatodendritic and postsynaptic 5-hydroxytryptamine-1A receptors are regulated differently in the rat brain.