Age-related changes in capsaicin-induced degeneration in rat brain.

Previous results indicate that the pattern of capsaicin-induced degeneration in the rat central nervous system is age-related. Experiments utilizing capsaicin's selective neurodegenerative effects to study the function of central neural circuits will therefore require a detailed understanding of capsaicin's central neurotoxicity in rats of different ages. The goal of this experiment was to characterize the degeneration induced in the rat brain by systemic treatment with capsaicin at different ages (10, 15, 20, 25, 30 or 75 days, or 11 months), using a cupric silver stain to label degenerating neurons. Results revealed degenerating cell bodies in the ventromedial brainstem in capsaicin-treated rats of all age groups, though they were more numerous in adult rats than in pups. In addition, many areas contained capsaicin-induced nerve terminal degeneration both in rat pups and in adult rats. These areas were the substantia gelatinosa of the spinal cord dorsal horn; the solitary tract; the nucleus of the solitary tract, visceral portion; the area postrema; the trigeminal nerve and spinal trigeminal nucleus; the medial nucleus of the inferior olive; the rostral, dorsomedial and dorsolateral interpeduncular subnuclei and overlying interfascicular nucleus; the supramammillary area; the lateral septal nucleus; the bed nucleus of the stria terminalis, anterior medial portion; the optic nerve and tract; the suprachiasmatic nucleus, ventroposterolateral portion; the magnocellular subnucleus of the ventrolateral geniculate nucleus; the intergeniculate leaf; the medial pretectal nucleus and the olivary pretectal nucleus. In several, but not all of these areas, the apparent density of degenerating terminals was significantly less in adult rats than in pups. In other brain sites, capsaicin-induced degeneration was observed only in rats younger than 30 days of age. These areas were the lateral habenula, medial part; the sphenoid nucleus; and the stria medullaris. Still other brain sites lost their sensitivity to capsaicin sometime between 30 and 75 days of age. These areas were the bed nucleus of the stria terminalis, medial posteromedial part; the medial preoptic nucleus, central part; the septohypothalamic nucleus; the ventral reuniens area; and the ventromedial hypothalamic nucleus. Adult rats 75 days and 11 months of age did not differ detectably in their response to capsaicin. Thus, loss or attenuation of capsaicin sensitivity is not progressive throughout life. It does not occur in all capsaicin-sensitive sites. Where it does occur, loss of sensitivity occurs prior to adulthood and follows a distinct and reproducible time course that may differ for different sites.