One important syndrome of psychiatric disorders in humans is catalepsy. Here, we created mice with different predispositions to catalepsy and analysed their pharmacological and behavioural properties.
EXPERIMENTAL APPROACHTwo mouse lines, B6-M76C and B6-M76B, were created by transfer of the main locus of catalepsy containing the 5-HT 1A receptor gene to the C57BL/6 genetic background. Behaviour, brain morphology, expression of key components of the serotoninergic system, and pharmacological responses to acute and chronic stimulation of the 5-HT 1A receptor were compared.
KEY RESULTSB6-M76B mice were not cataleptic, whereas 14% of B6-M76C mice demonstrated catalepsy and decreased depressive-like behaviour. Acute administration of the 5-HT 1A receptor agonist 8-OH-DPAT resulted in dose-dependent hypothermia and in decreased locomotion in both lines. Chronic 8-OH-DPAT administration abolished the 5-HT 1A receptor-mediated hypothermic response in B6-M76C mice and increased locomotor activity in B6-M76B mice. In addition, 5-HT metabolism was significantly reduced in the hippocampus of B6-M76C mice, and this effect was accompanied by an increased expression of the 5-HT 1A receptor.
CONCLUSIONS AND IMPLICATIONSOur findings indicate that transfer of the main locus of hereditary catalepsy containing the 5-HT 1A receptor from CBA mice to the C57BL/6 genetic background led to increased postsynaptic and decreased presynaptic functional responses of the 5-HT 1A receptor. This characteristic establishes the B6-M76C line as an attractive model for the pharmacological screening of 5-HT 1A receptor-related drugs specifically acting on either pre-or postsynaptic receptors.
LINKED ARTICLESThis article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc Abbreviations 5-HIAA, 5-hydroxyindoleacetic acid; 8-OH-DPAT, 8-hydroxy-2-(di-n-propylamino) tetralin; ASC, antidepressant-sensitive catalepsy; BDNF, brain-derived neurotrophic factor; EPM, elevated plus-maze test; FST, forced swim test; OF, open field test; Slc6a4, gene encoding 5-HT transporter; Tph2, tryptophan hydroxylase 2
Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (-2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild-type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (-1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (-2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.
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