+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Clozapine attenuates the locomotor sensitisation and the prepulse inhibition deficit induced by a repeated oral administration of Catha edulis extract and cathinone in rats



Clozapine attenuates the locomotor sensitisation and the prepulse inhibition deficit induced by a repeated oral administration of Catha edulis extract and cathinone in rats



Behavioural Brain Research 160(2): 365-373



Locomotor sensitisation and deficits in prepulse inhibition (PPI) induced by psychostimulants are two paradigms that have been widely studied as animal behavioural models of psychosis. Clozapine is one of the atypical antipsychotic agents which has been widely employed to reverse the aforementioned behavioural changes in these usual models. In this particular study, locomotor sensitisation and prepulse inhibition deficit were induced under the same context by intermittent oral administration of S-(-)-cathinone or Catha edulis extract in rats. The rats were then challenged by administration of the atypical antipsychotic drug, clozapine and were finally challenged with psychostimulants after 2-week of withdrawal. Locomotor activity and PPI were assessed and later analyses of the neurotransmitter levels were made. The results of this experiment show that repeated oral administration of cathinone or C. edulis extract enhanced locomotor and exploratory activity and lead to a gradual deficit in prepulse inhibition. This locomotor sensitisation and PPI deficit could be reversed by administration of clozapine. A challenge with psychostimulant on day 40 (i.e., after 2-week of withdrawal) resulted in a response similar to the initial exposure (day 1). Neurotransmitter level analyses showed a significant increase in the level of dopamine in the prefrontal cortex (p < 0.05). There was also a significant decrease in the level of 5-hydroxytryptamine (5-HT) in the nucleus accumbens (p < 0.05) and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the prefrontal cortex (p < 0.01). In the remaining regions (anterior and posterior striatum), there were no significant changes. In conclusion, this is the first study to demonstrate that repeated administration of C. edulis extract, or commercial cathinone, induces prepulse inhibition deficit and clozapine reverses both C. edulis or cathinone-induced sensitised locomotion and prepulse inhibition deficit.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011869894

Download citation: RISBibTeXText

PMID: 15863233

DOI: 10.1016/j.bbr.2005.01.002


Related references

Behavioural sensitisation following repeated intermittent oral administration of Catha edulis in rats. Behavioural Brain Research 156(2): 181-189, 2004

Reproductive parameters are differentially altered following subchronic administration of Catha edulis F. (Khat) extract and cathinone in male rats. Journal of Ethnopharmacology 134(3): 977-983, 2011

Short-term repeated dose biochemical effects of Catha edulis (khat) crude extract administration in rats. 2008

Repeated Catha edulis oral administration enhances the baseline aggressive behavior in isolated rats. Journal of Neural Transmission 113(5): 543-556, 2005

Catha edulis extract and its active principle cathinone induce ipsilateral rotation in unilaterally lesioned rats. Behavioural Pharmacology 17(7): 615-620, 2006

Acute oral administration of Khat (Catha edulis) aqueous extract elevates blood pressure and prolongs QT and QTC intervals in Wistar albino rats. Saudi Medical Journal 33(10): 1065-1072, 2012

Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat. Psychopharmacology 135(4): 401-406, 1998

Standardized extract of Ficus platyphylla reverses apomorphine-induced changes in prepulse inhibition and locomotor activity in rats. Behavioural Brain Research 293: 74-80, 2015

Evaluation of immunomodulatory activities of methanolic extract of khat (Catha edulis, Forsk) and cathinone in Swiss albino mice. Bmc Immunology 16: 9, 2015

Lamotrigine blocks the initiation and expression of repeated high-dose methamphetamine-induced prepulse inhibition deficit in rats. Neuroscience Letters 481(3): 183-187, 2010

Genotoxic effect of Catha edulis (khat) crude extract after sub-chronic administration in rats. Environmental Toxicology and Pharmacology 25(3): 298-303, 2008

Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. Pharmacology Biochemistry and Behavior 74(2): 279-286, 2003

Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. Pharmacology Biochemistry & Behavior 74(2): 279-286, 2003

Chronic nicotine administration attenuates quinpirole induced disruption in prepulse inhibition in rats. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 291 8, 2002

Subchronic oral administration of crude khat extract (Catha edulis forsk) induces schizophernic-like symptoms in mice. Bmc Complementary and Alternative Medicine 16: 153, 2016