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In vivo evaluation of effects of histamine H3 receptor antagonists on methamphetamine-induced hyperlocomotion in mice.
- Source :
-
Brain Research . Aug2020, Vol. 1740, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- • Histamine H 3 receptor antagonists attenuated METH-induced hyperlocomotion in mice. • H 1 antagonists inhibited effect of H 3 antagonists on METH-induced behavior. • H 3 antagonists may be considered as candidates for treatment of METH actions. A single administration with METH (3 mg/kg) induced a hyperlocomotion in male ICR mice. Pretreatment of mice with pitolisant, a histamine H 3 receptor antagonist (5 and 10 mg/kg), for 30 min showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle (saline)-pretreated subjects. Pretreatment of mice with the histamine H 3 receptor antagonists JNJ-10181457 (5 and 10 mg/kg) or conessine (20 mg/kg), also showed similar inhibitory effects on METH-induced hyperlocomotion, similar to pitolisant. No significant change in locomotion was observed in mice pretreated with pitolisant, JNJ-10181457, or conessine alone. The pitolisant (10 mg/kg) action on METH-induced hyperlocomotion was completely abolished by the histamine H 1 receptor antagonist pyrilamine (10 mg/kg), but not by the peripherally acting histamine H 1 receptor antagonist fexofenadine (20 mg/kg), the brain-penetrating histamine H 2 receptor antagonist zolantidine (10 mg/kg), or the brain-penetrating histamine H 4 receptor antagonist JNJ-7777120 (40 mg/kg). Pretreatment with a histamine H 3 receptor agonist immepip (10 mg/kg) augmented METH--induced behavior, including hyperlocomotion and stereotyped biting, and combined pretreatment with pitolisant (10 mg/kg) significantly attenuated stereotyped biting. These observations suggest that pretreatment with histamine H 3 receptor antagonists attenuate METH-induced hyperlocomotion via releasing histamine after blocking H 3 receptors, which then bind to the post-synaptic histamine receptor H 1 (but not H 2 or H 4). It is likely that activation of brain histamine systems may be a good strategy for the development of agents, which treat METH abuse and dependence. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANTIHISTAMINES
*HISTAMINE receptors
*HISTAMINE
*MICE
Subjects
Details
- Language :
- English
- ISSN :
- 00068993
- Volume :
- 1740
- Database :
- Academic Search Index
- Journal :
- Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 143415857
- Full Text :
- https://doi.org/10.1016/j.brainres.2020.146873