 |
STRIATAL DOPAMINE TERMINALS
RELEASE SEROTONIN AFTER 5-HTP PRETREATMENT: IN VIVO VOLTAMMETRIC
DATA.
Stamford JA,
Kruk ZL,
Millar J.
Department of Pharmacology, London Hospital Medical College, U.K.
Peripheral administration of
5-hydroxytryptophan (5-HTP) to rats causes 'wet dog' shakes and a
parallel elevation of brain serotonin (5-HT) levels. The increase in
5-HT concentration does not, however, correlate with the endogenous
5-HT innervation raising the possibility that some 5-HTP is
decarboxylated in non-serotonergic cells. In the present study we
used in vivo voltammetry to establish whether 5-HTP treatment led to
formation of 5-HT as a 'false transmitter' in striatal dopamine (DA)
neurons. Fast cyclic voltammetry at carbon fibre microelectrodes (CFMs)
was used to monitor striatal monoamine release following electrical
stimulation of the median forebrain bundle (MFB). In the absence of
any pretreatment DA was the sole compound released by stimulation.
However, when DA release was abolished with alpha-methyl-p-tyrosine
(AMPT), 5-HTP administration (after peripheral decarboxylase
inhibition) caused a dose-dependent release of 5-HT, confirmed by
the voltammetric characteristics. Central decarboxylase inhibition
prevented release indicating that 5-HTP itself was not released. By
monitoring reduction peaks it was possible to record DA and 5-HT
release simultaneously at a single CFM. While DA and 5-HT oxidised
at the same potential their reduction peaks were separated by
approximately 450 mV. It was shown, using this means, that 5-HT was
still detectable even when DA release was not abolished by AMPT. DA
and 5-HT release showed a significant positive correlation
suggesting that they were released from the same nerves. We conclude
that, after 5-HTP treatment, 5-HT can be released as a false
transmitter from striatal DA neurones.
|
|
