Electrophysiological characterization of 5-hydroxytryptamine2 receptors in the rat medial prefrontal cortex.
The aim of the present study was to characterize 5-hydroxytryptamine2 (5-HT2) receptors in the rat medial prefrontal cortex (mPFc) by single cell recording and microiontophoretic techniques. This was accomplished using 5-HT2 receptor agonists 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane [(+/-)-DOI] and 1-[2,5-dimethoxy-4-bromophenyl]-2-aminopropane [(+/-)-DOB]. DOI ejected at a low current (0.5 nA) potentiates glutamate (GLU)-induced activation of mPFc neurons and this effect is blocked by spiperone. At higher currents. DOI invariably inhibits GLU-induced neuronal activity. The microiontophoretic ejection of both DOI and DOB predominantly inhibits spontaneously active mPFc cells. The inhibitory action of DOI on spontaneously active cells is dose-dependent and is blocked by putative 5-HT2 receptor antagonists, with a rank order of potency as follows: ritanserin greater than metergoline approximately LY-53857 greater than spiperone greater than mesulergine greater than mianserin approximately ketanserin. Interestingly, ketanserin and mianserin only weakly block the effect of DOI. The suppressant action of DOI is probably not related to its interaction with 5-HT10 sites as spiperone, which has low affinity for these sites, potently blocks the effect of DOI. The suppressant effect of DOI is not blocked by other receptor antagonists such as BRL-43694 (5-HT3), (+/-)-pindolol (5HT 1a,1b, beta adrenergic, beta), prazosin (adrenergic1, alpha-1), pyrilamine (histamine1, H1), l-sulpiride (dopamine2, D2) or SR 95103 (gamma-aminobutyric acid, GABAA). Overall our results indicate that DOI predominantly inhibits mPFc cells in a direct manner and this effect is mediated by 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Ashby
C R
CR
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook.
Jiang
L H
LH
Kasser
R J
RJ
Wang
R Y
RY
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012970:Sodium Glutamate / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D004873:Ergolines; D011724:Pyridazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C003943:2,5-dimethoxy-4-bromoamphetamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C044796:2-(carboxy-3'-propyl)-3-amino-4-methyl-6-phenylpyridazinium chloride; D007650:Ketanserin; D008274:Magnesium; C032663:LY 53857; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D012970:Sodium Glutamate