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Monoamine Interactions Measured by Microdialysis in the Ventral Tegmental Area of Rats Treated Systemically with (±)‐8‐Hydroxy‐2‐(Di‐ n ‐Propylamino)tetralin
Author(s) -
Chen NianHang,
Reith Maarten E. A.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64041585.x
Subject(s) - microdialysis , ventral tegmental area , sulpiride , chemistry , medicine , serotonin , agonist , monoamine neurotransmitter , idazoxan , endocrinology , dopamine , 5 ht receptor , 8 oh dpat , antagonist , postsynaptic potential , norepinephrine , receptor , biology , prazosin , dopaminergic
The effect of (±)‐8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin (8‐OH‐DPAT), a selective serotonin 5‐HT 1A agonist, on levels of extracellular norepinephrine (NE), dopamine (DA), and 5‐HT (measured simultaneously) was investigated by microdialysis in the ventral tegmental area (VTA) of freely moving rats, and their behavioral activity was monitored. At 50 µg/kg s.c., 8‐OH‐DPAT reduced 5‐HT levels but enhanced NE and DA levels in VTA dialysate. These effects were not altered by pretreatment with systemic idazoxan (5 mg/kg i.p.), a selective α 2 antagonist, or local sulpiride (10 µ M ), a selective D 2 /D 3 antagonist. At 500 µg/kg s.c., 8‐OH‐DPAT further enhanced or more persistently reduced dialysate NE or 5‐HT content but had little effect on dialysate DA content. Its DA level‐increasing effect could be seen dramatically with local infusion of cocaine (30 µ M ) and, to a lesser extent, sulpiride (10 µ M ). Depletion of endogenous 5‐HT with p ‐chlorophenylalanine attenuated both the 5‐HT level‐reducing and DA level‐enhancing effects of 8‐OH‐DPAT without affecting its maximal NE effect and the locomotor‐stimulatory effect. Partial depletion of endogenous NE with N ‐(2‐chloroethyl)‐ N ‐ethyl‐2‐bromobenzylamine failed to change the monoamine response but diminished the locomotion induced by 8‐OH‐DPAT. These results suggested that (a) the low dose of 8‐OH‐DPAT may act at presynaptic 5‐HT 1A receptors to modulate 5‐HT and DA release, while acting at postsynaptic 5‐HT 1A receptors to modulate NE release; (b) the high dose of 8‐OH‐DPAT may activate D 2 receptors to offset its DA level‐increasing effect; and (c) the locomotor‐stimulatory effect of 8‐OH‐DPAT might be mediated primarily by postsynaptic 5‐HT 1A receptors and the NE system.