The guinea pig forced swim test as a new behavioral despair model to characterize potential antidepressants.
BACKGROUND
Behavioral despair is a model of high predictivity for antidepressant activity in murids. For some drug targets, guinea pigs exhibit a higher homology to their human counterparts compared to murids.


OBJECTIVE
In this paper, we established a model of behavioral despair namely, the forced swim test (FST) in guinea pigs.


METHODS
Male guinea pigs underwent the FST similar to rats. Animals received intraperitoneal injections of either vehicle or drugs 24, 4, and 0.5 h before testing. We tested the tricyclic antidepressants desipramine and amitriptyline, the monoamine oxidase inhibitor tranylcypromine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, and the neurokinin 1 (NK(1)) receptor antagonist, L-733,060, and for comparison the antipsychotic clozapine and the stimulant methamphetamine.


RESULTS
Desipramine (> or =3 mg/kg) and amitriptyline (>10 mg/kg) increased the latency to immobility (LTI) to greater than 230 s, and tranylcypromine (10 mg/kg) it to greater than 190 s. Paroxetine (>0.3 mg/kg) and fluoxetine (>10 mg/kg) also increased LTI significantly but only to greater than 120 s. Methamphetamine (3 mg/kg) completely eliminated immobility, whereas clozapine (5-20 mg/kg) had no effect. L-733,060 (10 mg/kg) increased LTI to 270 s. Doses producing significant effects in FST were investigated in the open field. Antidepressants did not affect locomotion, whereas methamphetamine induced hyperlocomotion.


CONCLUSIONS
We demonstrate the suitability of a modified procedure of the FST for a nonmurid species: the guinea pig. Known antidepressants showed similar effects as in rats and mice. It is interesting to note that the NK(1) antagonist L-733,060 increased forced swimming, suggesting its antidepressant potential. Thus, the guinea pig FST allows the study of antidepressant activity also in NK(1) antagonists that cannot be studied appropriately in murids.
Wicke
Karsten M
KM
Neuroscience Discovery Research, Abbott, 67008, Ludwigshafen, Germany. karsten.wicke@abbott.com
Rex
Andre
A
Jongen-Relo
Ana
A
Groth
Ilona
I
Gross
Gerhard
G
D000639:Amitriptyline / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000494:pharmacology*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D017374:Paroxetine / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013550:Swimming / Q000502:physiology / Q000523:psychology*; D014191:Tranylcypromine / Q000008:administration & dosage / Q000494:pharmacology
D000639:Amitriptyline; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D003024:Clozapine; D003891:Desipramine; D015507:Drugs, Investigational; D005473:Fluoxetine; D008694:Methamphetamine; D008996:Monoamine Oxidase Inhibitors; D017374:Paroxetine; D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; D014191:Tranylcypromine; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine