Nighttime
Changes in Norepinephrine and Melatonin Content And Serotonin
Turnover in Pineal Glands of Young and Old Rats Injected with
Freund’s Adjuvant
Pilar Cano, 1
Daniel P. Cardinali, 2
Fernando Chacon, 1
Carlos F. Reyes Toso, 2
Ana. I. Esquifino, 1
1.
Departamento de Bioquímica y Biología Molecular
III, and
2. Departamento de Fisiología, Facultad de Medicina,
Universidad de Buenos Aires, Buenos Aires, Argentina.
Submitted:
December 27, 2001
Accepted: December 31, 2001
Key
words:
Freundís adjuvant arthritis, aging, pineal gland, norepinephrine,
serotonin, melatonin
Abstract
OBJECTIVES: This study was performed to search for changes
in rat pineal function attributed to age and immunization
with Freund’s adjuvant.
METHODS:
Young (2 months) and old (18-20 months) Wistar rats were injected
s.c. with Freund’s adjuvant or its vehicle. Eighteen
days later, at the acute phase of arthritis, pineal concentration
of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA),
norepinephrine (NE) and melatonin was measured by high pressure
liquid chromatography at 4 different time intervals throughout
the nocturnal activity span.
RESULTS:
Old rats had the lowest pineal 5-HT and 5-HIAA content, the
decrease in 5-HIAA exceeding that of 5-HT; consequently, old
rats had the lowest 5-HIAA/5-HT ratio, an index of pineal
5-HT turnover. Although immunization did not affect globally
pineal 5-HT or 5-HIAA levels, significant interactions "immunization
x age" and "immunization x time" were found,
i.e., immunization augmented pineal 5-HT content at the beginning
of the activity span in young rats and at second half of the
activity span in young and old rats, and increased pineal
5-HIAA concentration in young rats at the second part of the
activity span only. Freund’s adjuvant treatment increased
pineal 5-HT turnover exclusively in old rats, an effect mainly
seen during the second part of the activity span. Old rats
exhibited the lowest pineal NE and melatonin levels, immunization
further depressing them.
CONCLUSION:
The effect of immunization with Freund’s adjuvant on
a number of pineal pre- and postsynaptic parameters are age-dependent.
Introduction
Adjuvant
arthritis in rats is usually induced by injection of mycobacterium
tubercle cell walls suspended in incomplete Freund’s
adjuvant [1]. A parallel clinical and behavioral study of
adjuvant-induced arthritis in the rat showed four stages in
the time-course of the disease: preclinical (first week),
acute (weeks 2-4), post-acute (weeks 5-8) and recovery (weeks
9-11) [2]. Adjuvant arthritis is widely employed as an experimental
paradigm to examine the relationships between the brain and
the immune system. In this model it was shown that cytokines
like interleukins 1, 2 or 6, granulocyte-macrophage colony-stimulating
factor or interferon-a are responsible for many of the symptoms
associated with inflammation ("sickness behavior")
[3,4].
In a previous study we examined young (50 days old) and old
(18 months old) Sprague-Dawley rats injected with mycobacterial
Freund’s adjuvant at preclinical and acute phases of
adjuvant’s arthritis [5]. At every post-injection interval
(6, 12 and 18 days after injection) old rats had significantly
lower nocturnal pineal melatonin levels. On day 18 of arthritis,
decreased levels of pineal melatonin were also seen in young
rats.
The
present study was undertaken to further analyze pineal pre-
and postsynaptic parameters during pineal nocturnal activation
in young and old arthritic Wistar rats. Pineal serotonin (5-HT)
and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured
by high pressure liquid chromatography (HPLC) at 4 time intervals
during the nocturnal activity span. In addition, pineal concentrations
of norepinephrine (NE) and melatonin were also measured by
HPLC.
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