Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/D3 antagonist sulpiride.
Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found 42 patterns of different composition occurring, on average, 520.90 ± 50.23 times per mouse in the histamine depleted (HD) group, whereas controls showed 12 different patterns occurring on average 223.30 ± 20.64 times. Exploratory and grooming behaviours clustered separately, and the increased pattern complexity involved exclusively exploratory patterns. To test the hypothesis of a histamine-dopamine interplay on behavioural pattern phenotype, non-sedative doses of the D2/D3 antagonist sulpiride (12.5-25-50 mg/kg) were additionally administered to different groups of HD mice. Sulpiride counterbalanced the enhancement of exploratory patterns of different composition, but it did not affect the mean number of patterns at none of the doses used. Our results provide new insights on the role of histamine on repetitive behavioural sequences of freely moving mice. Histamine deficiency is correlated with a general enhancement of pattern complexity. This study supports a putative involvement of histamine in the pathophysiology of tics and related disorders.
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy; S.O.D. Psichiatria, Azienda Ospedaliero-Universitaria Careggi, 50139 Firenze, Italy. Electronic address: a.santangelo@ymail.com.
Andrea
A
Santangelo
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy.
Gustavo
G
Provensi
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy.
Alessia
A
Costa
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy.
Patrizio
P
Blandina
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy; S.O.D. Psichiatria, Azienda Ospedaliero-Universitaria Careggi, 50139 Firenze, Italy.
Valdo
V
Ricca
Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università di Palermo, Corso Tukory 129, 90134, Palermo, Italy.
Giuseppe
G
Crescimanno
Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università di Palermo, Corso Tukory 129, 90134, Palermo, Italy.
Maurizio
M
Casarrubea
Maria Beatrice Passani Dipartimento di Scienze della Salute Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy.
M Beatrice
MB
Passani
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000172:deficiency*; D008297:Male; D051379:Mice; D011897:Random Allocation; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology*
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D006632:Histamine
Alpha-fluoromethilhistidine; Dopamine; Multivariate analysis; Sulpiride; T-pattern analysis