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Role of 5‐HT 3 receptors in basal and K + ‐evoked dopamine release from rat olfactory tubercle and striatal slices
Author(s) -
Zazpe A.,
Artaiz I.,
Río J.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17087.x
Subject(s) - olfactory tubercle , medicine , dopamine , endocrinology , ketanserin , agonist , chemistry , receptor antagonist , 5 ht receptor , receptor , serotonin , biology , striatum , antagonist
1 The present study was aimed at examining the role of 5‐HT 3 receptors in basal and depolarization‐evoked dopamine release from rat olfactory tubercle and striatal slices. [ 3 H]‐dopamine ([ 3 H]‐DA) release was measured in both brain regions and endogenous dopamine release from striatal slices was also studied. 2 The selective 5‐HT 3 receptor agonist 2‐methyl‐5‐HT (0.5–10μ m ) produced a concentration‐dependent increase in [ 3 H]‐DA efflux evoked by K + (20 μ m ) from slices of rat olfactory tubercle. 1‐Phenylbiguanide (PBG) and 5‐HT also increased K + ‐evoked [ 3 H]‐DA efflux. 3 5‐HT (1–100 μ m ) increased in a concentration‐dependent manner basal [ 3 H]‐DA release from olfactory tubercle and striatal slices as well as endogenous DA release from striatal slices. The selective 5‐HT 3 receptor agonists 2‐methyl‐5‐HT and 1‐phenylbiguanide were weaker releasing agents. In all cases, the release was Ca 2+ independent and tetrodotoxin insensitive. 4 5‐HT 3 receptor antagonists such as ondansetron, granisetron and tropisetron (0.2 μ m ) significantly blocked the enhanced K + ‐evoked [ 3 H]‐DA efflux from rat olfactory tubercle slices induced by 2‐methyl‐5‐HT. A ten fold higher concentration of the 5‐HT 2 receptor antagonist ketanserin was ineffective. 5 Much higher concentrations, up to 50 μ m , of the same 5‐HT 3 receptor antagonists did not block the increase in basal [ 3 H]‐DA release from striatal or olfactory tubercle slices induced by 5‐HT or the release of endogenous DA induced by 5‐HT from striatal slices. 6 The DA uptake blocker nomifensine (10 μ m ) did not modify the enhancement in K + ‐evoked [ 3 H]‐DA efflux from rat olfactory tubercle slices induced by 2‐methyl‐5‐HT. However, both nomifensine and cocaine significantly blocked the increase in basal dopamine release, either tritiated or endogenous, induced by 5‐HT. 7 These results indicate that 5‐HT 3 receptors only modulate DA release when the terminal fields of dopaminergic systems have been activated. In basal conditions, 5‐HT 3 receptor agonists enhance DA release through a carrier‐mediated mechanism. This may be of therapeutic relevance for the possible use of 5‐HT 3 receptor antagonists under conditions of abnormal activation of the dopaminergic system.