Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes.
OBJECTIVE
To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antagonist action on meso-accumbens-mPFC DA system.


METHODS
Single unit spontaneous firing activity was recorded in the nucleus accumbens (NAc) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates.


RESULTS
Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB-18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90 % of 6-OHDA-lesioned rats, while THPB-18 caused variable effects on the firing of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not D2 antagonist spiperone.


CONCLUSIONS
Similar to L-stepholidine, THPB-18 also possesses the D1 agonistic-D2 antagonistic dual action on the VTA-NAc DA system.
Fu
Yu
Y
State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Zhu
Zi-tao
ZT
Zhu
Xin-zu
XZ
Jin
Guo-zhang
GZ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000037:antagonists & inhibitors; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001552:Benzazepines / Q000037:antagonists & inhibitors; D001600:Berberine Alkaloids / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D011804:Quinolines / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013134:Spiperone / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000502:physiology
C416545:4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrzolo(3,4-g)quinoline; D001552:Benzazepines; D001600:Berberine Alkaloids; D065127:Dopamine D2 Receptor Antagonists; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C014845:berbine; D001058:Apomorphine