Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

May 1985

Abstract

Morphine and exogenous opioid peptides alter the development of central noradrenergic neurons damaged by neonatal treatment with the neurotoxin 6-hydroxydopa. Transection of the dorsal noradrenergic bundle (DNB) in neonatal rats produces nearly the same alteration in the developmental pattern. It was of interest to determine whether morphine or an exogenous opioid peptide (metenkephalin) was able to modify the recovery of noradrenergic neurons after neonatal surgical transection of the DNB. Neonatal rats were divided into two groups. Both groups received saline (0.85%) or naloxone (2.0 mg/kg) by the intraperitoneal (i.p.) route. In the first group the animals received an additional i.p. injection of either saline or morphine sulfate (3.33 mg/kg). The second group received an intraventricular injection of either saline, morphine (10 (mu)g/5 (mu)l), or methionine-enkephalin (25 (mu)g/5 (mu)l) ten minutes after the i.p. injection. Half the animals in these groups then received a DNB lesion, made with a blade 3mm (depth) by 5mm (width) at the level of the colliculi. At 6 weeks brains were removed for assay of norepinephrine (NE) content by a fluorometric method, and for determination of the rate of ('3)H-NE uptake, in order to assess noradrenergic fiber number. It was found that in the cerebellum both the ('3)H-NE uptake rate and NE content were significantly elevated by approximately 75% in the animals that received the lesion. The recovery in the anterior cortex (39%) was significantly greater than in the posterior cortex (27%), while recovery in the hippocampus (21%) was the least. This indicates a regional difference in recovery in the more distal projections of the DNB. Within the lesion group, however, there was no alteration in ('3)H-NE uptake rate nor NE content in any of the above regions with any of the drug treatments. Therefore, none of the drug treatments effectively altered the recovery from surgical transection of the DNB. It is suggested that opioids are capable of modifying neurotoxin damage per se, but not capable of modifying regeneration of noradrenergic neurons.

Document Type

Dissertation - Open Access

Included in

Pharmacology Commons

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