The guinea pig forced swim test as a new behavioral despair model to characterize potential antidepressants.

RATIONALE: 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. OBJECTIVES: In this paper, we established a model of behavioral despair namely, the forced swim test (FST) in guinea pigs. MATERIALS AND 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.

Running wheel activity is sensitive to acute treatment with selective inhibitors for either serotonin or norepinephrine reuptake.

RATIONALE: Most antidepressants (AD) directly or indirectly enhance the serotonergic tone in the CNS. Since the serotonin system is involved in both, the modulation of mood and motor behavior, it was reasoned that these drugs might also interfere with running wheel activity (RWA), a form of positively motivated motor behavior, which might be linked to pathological states like obsessive-compulsive disorder (OCD). OBJECTIVES: We used RWA to characterize ADs from all major classes. Effects on RWA were compared to effects on general locomotor activity (LOC) to control for unspecific effects on general locomotion. METHODS: Two hours before lights-off, mice were treated with either vehicle or one of the following AD: the selective serotonin reuptake inhibitors (SSRIs) citalopram (3-10 mg/kg), paroxetine (1-10 mg/kg) and fluoxetine (2-6.6 mg/kg), the selective norepinephrine reuptake inhibitor (SNRI) reboxetine (1-10 mg/kg), the monoamine oxidase (MAO) inhibitors tranylcypromine (1-3 mg/kg) and moclobemide (3-10 mg/kg), and the tricyclic ADs desipramine and imipramine (10-30 mg/kg, each). LOC and RWA were measured after lights-off. RESULTS: At the highest dose tested, all ADs, with the exception of the MAO inhibitors, significantly reduced RWA. Both tricyclics inhibited RWA only at doses that similarly affected LOC. In contrast, all SSRI and reboxetine inhibited RWA at doses that left LOC unaffected. CONCLUSIONS: SSRI and the SNRI reboxetine inhibit RWA at doses not suppressing LOC. RWA may represent a simple behavioral readout of positively motivated behavior that merits further attention for psychopharmacology.