The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 165 of 207
Octopamine
anastomosis or a sham operation. After each infusion, each animal was rated for
neurologic depression with a 17 point test battery. Although overt coma was not
induced, octopamine infusions severely depressed neurologic function.
Concentrations of noradrenaline, dopamine, and serotonin in the brain were
significantly decreased after the infusion of octopamine. Levels of noradrenaline
in the brain were significantly correlated with neurologic status and greater
depletion of noradrenaline was associated with greater neurologic depression. It
was thus demonstrated that infusing large amounts of the trace amine octopamine
depresses behavior in the rat and this depression is most closely associated with
depletion of stores of noradrenaline in the brain (23). The behavioral effects of
octopamine (50, 100 and 250 µg, icv) was studied in rats. Octopamine
significantly increased locomotor activity in all doses tested. Biochemical studies
showed that octopamine decreased the cerebral concentration of GABA and
reduced activity of glutamate decarboxylase in rats brain. Significant changes in
concentrations of NA and DA in brain of rats pretreated with octopamine were
found (24).
Octopamine (50-250 µg icv) activates both noradrenergic and dopaminergic
system of the rat. In rats pretreated with reserpine the stimulatory action of
octopamine was not inhibited, but even enhanced. Only selective destruction of
dopamine containing neurons (6-hydroxydopamine, 200 microgram ivc, given 1
hr after desipramine, 25 mg/kg ip) prevents octopamine-induced hyperactivity.
Octopamine depressed the noradrenaline level in the rat brain and increased
utilization of the amine, but did not affect the level and utilization of dopamine
(25). Intracerebroventricular administration of octopamine had opposite effects on
locomotor activity depending on whether or not the rats were subjected to
uncontrollable electric shocks. In unshocked rats, octopamine produced a large
decrease in locomotor activity, but when the rats were subjected to unsignalled
and uncontrollable electric shocks, a significant increase in locomotor activity
resulted. The latter effect was observed either when the shocks were applied
during the measurement of locomotor activity or when they were applied the day
before (conditioned suppression paradigm). These results support the hypothesis
of a neuromodulation of central noradrenergic transmission by octopamine (26).
Octopamine (100, 250 and 500 µg in rat, icv) exerted a stimulating effect on the
central nervous system in rats, which was evidenced by increased spontaneous
and basal motor activity, increased exploratory activity in the free-field test, and
also increased motor activity in reserpinised rats pretreated with nialamide.
Octopamine decreased the body temperature and prolonged the duration of
hexobarbital-induced sleep, and increased amphetamine-induced hyperactivity.
Locomotor agitation after octopamine injection was inhibited by
phenoxybenzamine and yohimbine in a dose of 10 mg/kg i.p. (27).
autonomic system: Octopamine is localized within sympathetic nerve endings
(28). The effect of octopamine on intestinal smooth muscle of rabbit isolated
jejunum has been studied. Octopamine induced a dose-dependent decrease of
muscle tone. Direct stimulation of adenylate cyclase by octopamine was
demonstrated using radioimmunoassay of cAMP. Via experimentation it was
suggested that octopamine acts on intestinal dopamine D1-receptor sites to
produce relaxation of rabbit jejunum through an increase of cAMP (12)
(octopamine dose was not mentioned in the abstract).