Dose- and duration-dependent effects of betahistine dihydrochloride treatment on histamine turnover in the cat.
Drugs interacting with the histaminergic system are currently used for vertigo treatment and it was shown in animal models that structural analogues of histamine like betahistine improved the recovery process after vestibular lesion. This study was aimed at determining the possible dose and duration effects of betahistine treatment on histamine turnover in normal adult cats, as judged by the level of messenger RNA for histidine decarboxylase (enzyme synthesizing histamine) in the tuberomammillary nuclei. Experiments were conducted on betahistine-treated cats receiving daily doses of 2, 5, 10, or 50 mg/kg during 1 week, 3 weeks, 2 months, or 3 months. The 1-week, 3-week, and 2- and 3-month treatments correspond to the acute, compensatory, and sustained compensatory stages of vestibular compensation, respectively. The lowest dose (2 mg/kg) given the longest time (3 months) was close to the dosage for vestibular defective patients. Data from the experimental groups were compared to control, untreated cats and to placebo-treated animals. The results clearly show that betahistine dihydrochloride administered orally in the normal cat interferes with histamine turnover by increasing the basal expression level of histidine decarboxylase mRNA of neurons located in the tuberomammillary nuclei of the posterior hypothalamus. The effects were both dose- and time-dependent. In conclusion, compensation of both static and dynamic deficits is subtended by long-term adaptive mechanisms that could be facilitated pharmacologically using betahistine dihydrochloride.
Tighilet
Brahim
B
UMR 6149 Université de Provence/CNRS Neurobiologie Intégrative et Adaptative, Pôle 3C Comportement, Cerveau, Cognition, Centre de St Charles, Case B, 3 Place Victor Hugo, 13331 Marseille Cedex 3, France. tighilet@up.univ-mrs.fr
Trottier
Suzanne
S
Lacour
Michel
M
D000704:Analysis of Variance; D000818:Animals; D001621:Betahistine / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006632:Histamine / Q000378:metabolism*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D015837:Vestibular Diseases / Q000188:drug therapy / Q000503:physiopathology
D017442:Histamine Agonists; D012333:RNA, Messenger; D006632:Histamine; D006640:Histidine Decarboxylase; D001621:Betahistine