Behavioral tolerance to and withdrawal from multiple fluoxetine administration.
The objective of this study was to characterize the lasting effects of fluoxetine on the locomotor behavior of rats using a computerized activity-monitoring system. Challenge dosages (8, 16, and 24 mg/kg i.p.) of fluoxetine 2 h into the dark phase resulted in dose-dependent suppression of locomotor activity for 4 h following injection. Escalating (10-30 mg/kg i.p.) semidaily fluoxetine administration for the next five days resulted in decreasing locomotor activity during the multiple-administration period relative to saline control. Circadian activity patterns at the conclusion of the regimen were unchanged in shape, but featured uniform decreases in locomotor activity at every hour which were more significant during the phase. Upon discontinuation, fluoxetine-treated rats showed a significant increase in activity during the first 4 h following the first "missed" dose which was not seen in subsequent washout. Ninety-six h after the final maintenance dose, the initial three dosages were readministered, and the locomotor activity suppression in response to the rechallenge dose of fluoxetine was significantly lessened compared to initial challenge. These findings suggest that tolerance and withdrawal were obtained.
Bjork
J M
JM
Department of Neurobiology and Anatomy, University of Texas-Houston, Medical School of Houston, 77025, USA.
Gaytan
O
O
Patt
N
N
Swann
A C
AC
Dafny
N
N
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors