Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test.
BACKGROUND
The forced swimming test (FST) is a behavioral test in rodents that predicts the clinical efficacy of many types of antidepressant treatments. Recently, a behavior sampling technique was developed that scores individual response categories, including swimming, climbing and immobility. Although all antidepressant drugs reduce immobility in the FST, at least two distinct active behavioral patterns are produced by pharmacologically selective antidepressant drugs. Serotonin-selective reuptake inhibitors increase swimming behavior, while drugs acting primarily to increase extracellular levels of norepinephrine or dopamine increase climbing behavior. Distinct patterns of active behaviors in the FST may be mediated by distinct neurotransmitters, but this has not been shown directly.


OBJECTIVE
The present study examined the role of serotonin in mediating active behaviors in the forced swimming test after treatment with two antidepressant drugs, the selective serotonin reuptake inhibitor, fluoxetine and the selective norepinephrine reuptake inhibitor, desipramine.


METHODS
Endogenous serotonin was depleted by administering para-cholorophenylalanine (PCPA, 150 mg/kg, IP.) to rats 72 h and 48 h prior to the swim test. Fluoxetine (10 mg/kg, SC) or desipramine (10 mg/kg, SC) was given three times over a 24-h period prior to the FST. Behavioral responses, including immobility, swimming and climbing, were counted during the 5-min test.


RESULTS
Pretreatment with PCPA blocked fluoxetine-induced reduction in immobility and increase in swimming behavior during the FST. In contrast, PCPA pretreatment did not interfere with the ability of desipramine to reduce immobility and increase climbing behavior.


CONCLUSIONS
Depletion of serotonin prevented the behavioral effects of the selective serotonin reuptake inhibitor fluoxetine in the rat FST. Furthermore, depletion of serotonin had no impact on the behavioral effects induced by the selective norepinephrine reuptake inhibitor, desipramine. The effects of antidepressant drugs on FST-induced immobility may be exerted by distinguishable contributions from different neurotransmitter systems.
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Departments of Psychiatry and Pharmacology, University of Pennsylvania, 3620 Hamilton Walk, 320 John Morgan Building, Philadelphia, PA 19104, USA. page@pharm.med.upenn.edu
Detke
M J
MJ
Dalvi
A
A
Kirby
L G
LG
Lucki
I
I
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003891:Desipramine / Q000627:therapeutic use*; D010134:Fenclonine; D005473:Fluoxetine / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D013312:Stress, Physiological / Q000188:drug therapy*; D013550:Swimming
D000928:Antidepressive Agents; D012702:Serotonin Antagonists; D005473:Fluoxetine; D012701:Serotonin; D010134:Fenclonine; D003891:Desipramine