Involvement of the brain serotonergic system in the locomotor stimulant effects of chlorpheniramine in Wistar rats: implication of postsynaptic 5-HT1A receptors
Φόρτωση...
Ημερομηνία
Συγγραφείς
Karamanakos, P. N.
Pappas, P.
Marselos, M.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Behav Brain Res
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Antihistamines, such as chlorpheniramine (CPA), are lipophilic agents which readily cross the blood-brain barrier, producing sedation in 10-25% of users. However, with excessive doses instead of sedation a stimulating action has been reported. The aim of the present study was to investigate the influence of CPA on the locomotor activity of the rat in relation to its effects on brain biogenic monoamines. Wistar rats were given CPA (40 mg/kg, i.p.) and locomotor activity was measured in a photocell cage. Body temperature was also monitored. In addition, in three brain subregions (striatum, hypothalamus, and midbrain), the levels of 5-HT, NA, DA, as well as their metabolites, were determined by HPLC. Soon after injection, CPA produced a significant increase in locomotor activity, while a hypothermic response was also induced. In striatum and hypothalamus, which are known to be rich in postsynaptic 5-HT1A receptors, we found a significant time-dependent increase of 5-HT, correlated with the clearly enhanced locomotor activity of the animals. On the contrary, in midbrain, where presynaptic 5-HT1A receptors are dominating, no changes could be detected in 5-HT. In all three brain regions measured, 5-HIAA levels were decreased. The levels of the other brain monoamines were only marginally affected. In support of a role in receptor specificity, pretreatment with the 5-HT1A receptor agonist 8-OH-DPAT (1.25 mg/kg, i.p., two times) or with the 5-HT(1A/B) receptor antagonist pindolol (30 mg/kg, i.p., two times), enhanced or blocked, respectively, the hyperlocomotion induced by CPA. These findings suggest that the central serotonergic system may play a key role in the locomotor stimulant effects of CPA in the rat. Moreover, this behavioral component of CPA seems to be primarily mediated via the postsynaptic 5-HT1A receptors.
Περιγραφή
Λέξεις-κλειδιά
3,4-Dihydroxyphenylacetic Acid/metabolism, 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology, Animals, Behavior, Animal/drug effects, Body Temperature/drug effects, Brain/anatomy & histology/*metabolism, Brain Chemistry, Chlorpheniramine/*pharmacology, Chromatography, High Pressure Liquid/methods, Dopamine/metabolism, Histamine H1 Antagonists/pharmacology, Homovanillic Acid/metabolism, Hydroxyindoleacetic Acid/metabolism, Male, Motor Activity/*drug effects, Norepinephrine/metabolism, Rats, Rats, Wistar/*metabolism, Receptor, Serotonin, 5-HT1A/*physiology, Serotonin/*metabolism, Serotonin 5-HT1 Receptor Agonists, Serotonin Receptor Agonists/pharmacology, Species Specificity, Statistics, Nonparametric, Time Factors
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/14684260
http://ac.els-cdn.com/S0166432803001931/1-s2.0-S0166432803001931-main.pdf?_tid=0e54be90cdf68320f664977d12f09410&acdnat=1333002316_6bd99aae4ecd3201a6784c48a9fb941b
http://ac.els-cdn.com/S0166432803001931/1-s2.0-S0166432803001931-main.pdf?_tid=0e54be90cdf68320f664977d12f09410&acdnat=1333002316_6bd99aae4ecd3201a6784c48a9fb941b
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής