The short- and long-term effects of neonatal exposure to bombesin and/or (D-phenylalanine(6),Psi leucine(13)-chloroparpylamid(14))BN(6-14), a bombesin receptor antagonist.

Abstract

Bombesin (BN) is a tetradecapeptide originally isolated from the skin of the European anuran, Bombina bombina. The overall purpose of these studies was to gain some insight into the possible physiological role(s) of BN-like peptides during ontogeny. The specific objectives of these experiments were: (1) to characterize the behavioural response(s) of developing rats to centrally and peripherally administered BN; and (2) to examine the short- and long-term consequences of neonatal exposure to BN and/or (D-Phe$\sp6, \Psi$Leu$\sp $-Cpa$\sp $) BN(6-14), a BN receptor antagonist. Subcutaneous (s.c.) administration of BN (1-10 mg/kg) elicited grooming in rat pups of 1-10 days of age and the magnitude of this response decreased as a function of age. The decrease in behavioural sensitivity to BN probably reflected the declining permeability of the blood-brain barrier to BN. Indeed, intracerebroventricular (i.c.v.) injection of BN (0.01-1.0 ug) dose-dependently induced grooming in rat pups up to 20 days of age. Furthermore, the 20 day old rat pups were the most and the 1 day olds the least sensitive to i.c.v. BN. Subchronic neonatal exposure to BN (5 or 10 mg/kg; s.c., twice daily for the first 8 postnatal days) had no effect on later behaviour displayed under mildly stressful or novel conditions or activity elicited by the open field or elevated plus maze. However, both saline and the high dose of BN (10 mg/kg) pretreatments increased adult sensitivity to central BN (0.1 ug; i.c.v.) as compared to non-injected but neonatally handled controls or those rats neonatally pretreated with the lower dose of BN (5 mg/kg). Subchronic neonatal exposure to (D-Phe$\sp6, \Psi$Leu$\sp $-Cpa$\sp $) BN(6-14), a BN receptor antagonist, under a regime of 5 and 10 mg/kg; s.c. twice daily for the first 8 postnatal days, had no effect on the later expression of behaviour under mildly stressful or novel conditions or activity elicited on the open field test. However, neonatal pretreatment with the higher dose of (D-Phe$\sp6, \Psi$Leu$\sp $-Cpa$\sp $) BN(6-14) (10 mg/kg), had an apparent anxiolytic effect on later behaviour in the elevated plus maze. In conclusion, these data indicate that BN receptors in the rat c.n.s. are pharmacologically functional early in ontogeny, prior to the availability of measurable amounts of BN-like peptides. Behaviour induced by BN (s.c. or i.c.v.) reflects the status of motor capabilities of the developing organism and BN may serve as a useful pharmacological tool for investigating the ontogeny of grooming/scratching behaviour(s). Systems utilizing BN-like peptides are, to a degree, plastic early in ontogeny and altered adult sensitivity to BN i.c.v. can be achieved via subchronic exposure to BN during infancy. Endogenous BN-based mechanisms did not appear to play a role in the development and/or expression of behaviour(s) elicited under mildly stressful or novel conditions but may influence the behavioural regulation of anxiety-like responses (as measured by the elevated plus maze). (Abstract shortened by UMI.)