Striatal dopamine terminals release serotonin after 5-HTP pretreatment: in vivo voltammetric data.
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.
Stamford
J A
JA
Department of Pharmacology, London Hospital Medical College, U.K.
Kruk
Z L
ZL
Millar
J
J
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D004563:Electrochemistry; D005625:Frontal Lobe / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006916:5-Hydroxytryptophan; D004298:Dopamine