Motor disturbances and neurotoxicity induced by centrally administered somatostatin and vasopressin in conscious rats: interactive effects of two neuropeptides
1988; Elsevier BV; Volume: 445; Issue: 1 Linguagem: Inglês
10.1016/0006-8993(88)91080-3
ISSN1872-6240
AutoresCarey D. Balaban, Duane A. Fredericks, John N.D. Wurpel, Walter B. Severs,
Tópico(s)Sleep and Wakefulness Research
ResumoBarrel rotation (BR) is an abnormal, long-axis rotation induced by intracerebroventricular (i.c.v.) injections of peptides, including somatostatin (SRIF) and arginine-vasopressin (AVP). This study examined the effects of two i.c.v. doses of SRIF and combined injections of SRIF and AVP in conscious, adult Wistar and Sprague-Dawley rats. Mortality after i.c.v. SRIF was dose-dependent: 0/16 rats died after a 20 μg dose, while 2143 died after 40 μg SRIF. On the other hand, BR incidence was similar after the two doses, but the hazard function of the BR latency data was shifted to the left by the higher dose. Although the incidence data imply that BR and mortality are independent, the hazard function of BR latency data is predictive of mortality. An interaction study employing a combined i.c.v. dose of 20 μg SRIF and 0.5 μg AVP established that the effects add non-linearly. This is illustrated by a marked increment in mortality (016for 20 μg SRIF, 125for μgAVP and1218for SRIF + AVP). The hazard plot shows a similar, non-linear interaction. In addition, SRIF, but not AVP, produced a characteristic pattern of Purkinje cell death in cerebellar regions projecting to the fastigial and lateral vestibular nuclei. These results imply that SRIF and AVP act at independent sites to produce BR and mortality, and that the effects summate non-linearly at a common central site. This raises the issue of whether these neuropeptides, endogenous in human CSF, interact to produce similar biological effects.
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