Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI.
Systemic, intra-raphe and microiontophoretic administration of the 5-hydroxytryptamine (5-HT)1C/5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) inhibited the firing of 5-HT neurones in the dorsal raphe. DOI administered systemically and directly into the raphe also decreased the extracellular concentration of 5-hydroxytryptamine (5-HT) in the frontal cortex. In contrast, the administration of DOI directly into the frontal cortex did not significantly alter the concentration of frontal cortical extracellular 5-HT. The reduction of the firing rate of 5-HT neurons in the dorsal raphe and extracellular 5-HT concentration in the frontal cortex induced by systemic administration of DOI could not be blocked by the 5-HT2 antagonist ketanserin, ritanserin (5-HT2/5-HT1C antagonist) or the putative 5-HT1A antagonist, pindolol. These results suggest that the inhibition of 5-HT neuronal firing seen with administration of DOI is mediated via an action within the dorsal raphe and at least in close proximity to the 5-HT neurone cell bodies. The decrease in frontal cortical extracellular concentration of 5-HT release was not due to a direct action in the frontal cortex itself and may possibly be as a result of the decrease in the firing rate of the 5-HT neurones in the dorsal raphe. The mechanism of action of DOI to produce these effects is, however, unclear and warrants further investigation.
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
J C
JC
Garratt
E J
EJ
Kidd
I K
IK
Wright
C A
CA
Marsden
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D000662:Amphetamines; D012701:Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine