Chlorpromazine Inhibition of Dehydration-Induced Histological Changes in the Hypothalamic Neurosecretory System of the Musk Shrew, Suncus murinus L.

Abstract

SynopsisThe effect of chlorpromazine (CPZ) on the histology of the hypothalamic neurosecretory system (HNS) was investigated in Suneus murinus L. which were injected with hypertonic saline. Chronic saline treatment brought about characteristic histological changes in the neurons of the paraventricular nucleus (PVN) and depletion of neurosecretory material (NSM) from the cytoplasm, stalk median eminence (SME) and the neural lobe (NL). Acute saline treatment affected the neurons of both the PVN and the supraoptic nucleus (SON); there was no detectable depletion of NSM from SME and NL. Pretreatment with or simultaneous administration of CPZ prevented the appearance of the histological changes in the HNS that normally follow chronic and acute treatments with hypertonic saline. Since the hypertonic saline-induced histological changes in the HNS are regarded as morphological manifestations of increased secretion of the antidiuretic hormone (ADH), the inhibition, by CPZ, of these changes is interpreted as providing histological evidence in favour of the diuretic effect of the drug.The available information on the effect of chlorpromazine (CPZ) on the secretion of the antidiuretic hormone (ADH) is somewhat contradictory (see Gaunt et al., 1963;de Wied, 1967). Many investigators (e.g., Kovacs et al., 1957;Bachrach et al., 1958;Supek et al., 1960;Tiwari et al., 1960;Batrinos and de Verbizier, 1962;Boris and Stevenson, 1964;Jacobson, 1965) have reported that in mammals CPZ exerts an antidiuretic effect by stimulation of ADH release from the neurohypophysis. On the other hand, others (e.g., Moyer, 1955a, b;Moyer et al., 1954;Shibusawa et al., 1955;Parrish and Levine, 1956;Kivalo et al., 1957Kivalo et al., , 1958Smith et al., 1958) have reported that CPZ has diuretic effect in mammals. It is also reported (Moses, 1964;Boris and Stevenson, 1967;Milmore and Hammerman, 1969) that CPZ blocks the antidiuretic effect which occurs in response to dehydration; however, Bachrach et al.(1958) and Scultety et al.(1958) found that CPZ was ineffective in blocking the dehydrationinduced antidiuresis.A few studies have also been made concerning the effect of CPZ on the quantity of neurosecretory material (NSM) in the hypothalamic neurosecretory system (HNS). Kivalo et al.(1958) found that administration of 25 mg of CPZ per kg for 7 days to normal rats reduced the NSM in the neural lobe (NL), but not in the supraoptic (SON) and paraventricular (PVN) nuclei. Working with lower doses (10mg per kg daily for 6 days), Bachrach et al.(1958) found that CPZ had no effect on the quantity of NSM in the neurohypophysis. Dehydration-induced depletion of NSM was not inhibited by this treatment. However, Soulairac and Soulairac (1963) reported that administration of CPZ (3 mg/day/ animal for 10 days) to rats caused an increase in the quantity of NSM in all regions