Pharmacological profile of encounter-induced hyperactivity in isolation-reared mice.
We have recently found that isolation-reared mice show hyperactivity during an encounter with an intruder. However, it is not known whether encounter-induced hyperactivity may model some aspects of psychiatric disorders. The present study examined the pharmacological profile of encounter-induced hyperactivity in isolation-reared mice. Encounter-induced hyperactivity was reduced by acute administration of various antidepressants including the tricyclic antidepressant desipramine (10 mg/kg), the selective serotonin (5-HT) reuptake inhibitors fluvoxamine (10 mg/kg) and paroxetine (10 mg/kg), the 5-HT/noradrenaline reuptake inhibitors venlafaxine (10 mg/kg) and duloxetine (10 mg/kg), the antipsychotic drug risperidone (0.01 mg/kg), the 5-HT2 antagonist ritanserin (1 mg/kg), and the glucocorticoid receptor antagonist RU-43044 (30 mg/kg). The α2 adrenoceptor agonist clonidine (0.03 mg/kg) and the 5-HT4 receptor agonist BIMU8 (30 mg/kg) also reduced encounter-induced hyperactivity. The effect of desipramine was blocked by the α2 adrenoceptor antagonist idazoxan (0.3 mg/kg). The effect of fluvoxamine was blocked by the 5-HT4 receptor antagonist GR125487 (3 mg/kg), but not the 5-HT1A receptor antagonist WAY100635 (1 mg/kg), the 5-HT3 receptor antagonist azasetron (3 mg/kg), or the 5-HT6 receptor antagonist SB399885 (3 mg/kg). The effect of venlafaxine was blocked by the simultaneous administration of idazoxan (0.3 mg/kg) and GR125487 (3 mg/kg), but not by either compound alone. These findings suggest that encounter-induced hyperactivity in isolation-reared mice is a robust model for testing the pharmacological profile of antidepressants, although the range of antidepressants tested is limited and some non-antidepressants are also effective. The present study also shows a key role of α2 and 5-HT4 receptors in the antidepressant effect in this model.
aLaboratory of Medicinal Pharmacology bLaboratory of Molecular Neuropharmacology ciPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences dUnited Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui eDepartment of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, Japan.
Shigeru
S
Hasebe
Yukio
Y
Ago
Saki
S
Nishiyama
Satoshi
S
Oka
Hitoshi
H
Hashimoto
Kazuhiro
K
Takuma
Toshio
T
Matsuda
D000818:Animals; D021461:Animals, Outbred Strains; D001562:Benzimidazoles / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006889:Hydroxycorticosteroids / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009483:Neuropsychological Tests; D010078:Oxazines / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018967:Risperidone / Q000494:pharmacology; D016713:Ritanserin / Q000494:pharmacology; D012919:Social Behavior; D012934:Social Isolation / Q000523:psychology*; D013449:Sulfonamides / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006889:Hydroxycorticosteroids; D007211:Indoles; D010078:Oxazines; D010879:Piperazines; D011619:Psychotropic Drugs; D011725:Pyridines; C503990:SB 399885; D013449:Sulfonamides; C070189:(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide; C085917:RU 43044; D016713:Ritanserin; D017374:Paroxetine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C070671:azasetron; D000069470:Venlafaxine Hydrochloride; D000068736:Duloxetine Hydrochloride; D018967:Risperidone; D016666:Fluvoxamine; D003891:Desipramine; D019329:Idazoxan; C082871:GR 113808