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Effects of chronic fluoxetine treatment in the presence and absence of (±)pindolol: a microdialysis study
Author(s) -
Dawson L A,
Nguyen H Q,
Smith D I,
Schechter L E
Publication year - 2000
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 - 10.1038/sj.bjp.0703378
Subject(s) - fluoxetine , microdialysis , pindolol , reuptake inhibitor , extracellular , agonist , chemistry , pharmacology , endocrinology , serotonin , medicine , 5 ht receptor , antagonist , extracellular fluid , 8 oh dpat , receptor , biochemistry
Using in vivo microdialysis in the frontal cortex of the freely moving rat we evaluated the effects of chronic treatment with the serotonin specific reuptake inhibitor (SSRI) fluoxetine in the presence and absence of the 5‐HT 1A /β‐adrenergic antagonist (±)pindolol. Chronic vehicle treated animals produced no significant response to a challenge with fluoxetine (10 mg kg −1 ) on day 8 and 15. Alternatively, a significant ( P <0.05) decrease in extracellular 5‐HT was observed in control animals upon challenge with the 5‐HT 1A agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT; 0.03 and 0.1 mg kg −1 ). Conversely, animals treated with fluoxetine (10 mg kg −1 o.d.) for 7 and 14 days produced a significant ( P <0.05) 2 fold increase in extracellular 5‐HT when challenged with fluoxetine (10 mg kg −1 ) on day 8 and 15. Moreover, no significant decrease in extracellular 5‐HT was observed upon challenge with either dose of 8‐OH‐DPAT. Animals chronically treated with (±)pindolol (10 or 20 mg kg −1 b.i.d.) produced a significant dose‐related increase in extracellular 5‐HT upon challenge with fluoxetine on day 15 only. Furthermore, both doses produced a significantly blunted response to the low dose challenge of 8‐OH‐DPAT (0.03 mg kg −1 ). In addition, 20 mg kg −1 (±)pindolol treated animals also had no response to the higher 0.1 mg kg −1 dose of 8‐OH‐DPAT. Animals treated for 14 days with a combination of (±)pindolol (10 or 20 mg kg −1 ) and fluoxetine were not significantly different from vehicle treated animals when challenged with fluoxetine or 8‐OH‐DPAT. Taken together it would therefore appear that although (±)pindolol alone has sufficient intrinsic activity to produce a desensitization of the 5‐HT 1A receptor, when given in combination with fluoxetine it is able to prevent the desensitization induced by not only fluoxetine but also itself. This may suggest that the clinical augmentation of antidepressant action by pindolol, when co‐administered with a SSRI, is via antagonism of the 5‐HT 1A receptor.British Journal of Pharmacology (2000) 130 , 797–804; doi: 10.1038/sj.bjp.0703378