Prior work has established that hypoglossal motoneurons (HMs) change postnatally in their response to serotonin (5-HT), in part as a result of a decline in expression of 5-HT1A receptors. In the current study, two issues were addressed. First, using in situ hybridization we found that transient expression of 5-HT1A receptors occurs in other populations of brainstem (facial and trigeminal) and spinal (cervical and lumbar) metoneurons. Second. the participation of motoneuronal afferent (serotonergic) and efferent (neuromuscular) innervation in inducing and maintaining this decline in expression was investigated. Serotonergic innervation of the hypoglossal nucleus (nXII) was disrupted in neonatal rats by intra-cisternal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). and 5-MT1A receptor mRNA levels in nXII from these rats were assayed at postnatal day 21. In spite of an almost complete loss of serotonergic fibers in the region, the postnatal decrease in 5-HT1A receptor expression by HMs still occurred. To test for potential regulation by target-derived factors or by nerve injury, receptor mRNA levels were assayed after unilateral transection of the hypoglossal nerve in adult rats. Though this treatment resulted in re-induction of developmentally transient expression of the p75 neurotrophin receptor, 5-HT1A receptor expression remained low. Thus, neonatal expression of 5-HT1A receptors appears to be common to somatic motoneurons, but we found no evidence for changes in serotonergic innervation in influencing this expression, nor did we find evidence for its regulation by peripheral factors. (C) 2000 Elsevier Science B.V. All rights reserved.