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Published in: Metabolic Brain Disease 2/2014

01-06-2014 | Original Paper

Acute and sub-chronic effects of purified cathinone from khat (Catha edulis) on behavioural profiles in vervet monkeys (Chlorocebus aethiops)

Authors: Albert W. Nyongesa, Jemimah A. Oduma, Motohiro Nakajima, Hesbon O. Odongo, Pius A. Adoyo, Mustafa al’Absi

Published in: Metabolic Brain Disease | Issue 2/2014

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Abstract

We investigated the cumulative effects of cathinone on behavioural alterations in single-caged vervet monkeys. Fourteen adult vervets were divided into tests (12 animals) and controls (2 animals), and exposed to escalating doses of cathinone at alternate days of each week for 4 months in presence and absence of cage enrichment. One month of pre-treatment phase served to establish baseline values. Composite behavioural scores of aggression, anxiety, abnormal responses, withdrawal and appetite loss were done. A series of repeated measures analysis of variances were conducted to examine the extent to which cathinone administration was associated with patterns of changes in behavioural data. Results indicate a dose-dependent effect of cathinone on increases of aggression, anxiety, abnormal responses, withdrawal, and appetite loss. The findings demonstrate that at high doses and long-term exposure, cathinone causes behavioural alterations probably via changes in presynaptic striatal dopamine system.
Literature
go back to reference Al-Bekairi AM, Abulaban FS, Qureshi S, Shah AH (1991) The toxicity of Catha edulis (Khat). A review. Fitoterapia LXII:291–300 Al-Bekairi AM, Abulaban FS, Qureshi S, Shah AH (1991) The toxicity of Catha edulis (Khat). A review. Fitoterapia LXII:291–300
go back to reference Banjaw MY, Miczek K, Schmidt WJ (2005) Repeated Catha edulis oral administration enhances the baseline aggressive behaviour in isolated rats. J Neural Transm 113:543–556 Banjaw MY, Miczek K, Schmidt WJ (2005) Repeated Catha edulis oral administration enhances the baseline aggressive behaviour in isolated rats. J Neural Transm 113:543–556
go back to reference Bayne KA (1989) Nylon balls revisited. Lab Primate Newsl 28:5–6 Bayne KA (1989) Nylon balls revisited. Lab Primate Newsl 28:5–6
go back to reference Berman SM, Kuczenski R, McCracken JT, London ED (2009) Potential adverse effects of amphetamine treatment on brain and behaviour: a review. Mol Psychiatry 14:123–142PubMedCentralPubMedCrossRef Berman SM, Kuczenski R, McCracken JT, London ED (2009) Potential adverse effects of amphetamine treatment on brain and behaviour: a review. Mol Psychiatry 14:123–142PubMedCentralPubMedCrossRef
go back to reference Calcagnetti DJ, Schechter MD (1993) Place preference for the psychostimulant-cathinone is blocked by pretreatment with a dopamine release inhibitor. Prog Neuro-Psychopharmacol Biol Psychiatry 17:637–649CrossRef Calcagnetti DJ, Schechter MD (1993) Place preference for the psychostimulant-cathinone is blocked by pretreatment with a dopamine release inhibitor. Prog Neuro-Psychopharmacol Biol Psychiatry 17:637–649CrossRef
go back to reference Castner SA, Goldman-Rakic PS (1999) Long-lasting psychotomimetic consequences of repeated low-dose amphetamine exposure in rhesus monkeys. Neuropsychopharmacology 20:10–28PubMedCrossRef Castner SA, Goldman-Rakic PS (1999) Long-lasting psychotomimetic consequences of repeated low-dose amphetamine exposure in rhesus monkeys. Neuropsychopharmacology 20:10–28PubMedCrossRef
go back to reference Charney DS, Drystal JJ, Southwick SM, Nagy LM, Woods SW, Heninger GR (1990) Serotonin function in panic and generalized anxiety disorders. Psychiatr Ann 20:593–604 Charney DS, Drystal JJ, Southwick SM, Nagy LM, Woods SW, Heninger GR (1990) Serotonin function in panic and generalized anxiety disorders. Psychiatr Ann 20:593–604
go back to reference Clinical Practice Guideline (2001) Treatment of the school-aged child with attention deficit/hyperactivity disorder. Pediatrics 108:1033–1044CrossRef Clinical Practice Guideline (2001) Treatment of the school-aged child with attention deficit/hyperactivity disorder. Pediatrics 108:1033–1044CrossRef
go back to reference Cox G, Rampes H (2003) Adverse effects of khat. A review. Adv Psychiatr Treat 9:456–463CrossRef Cox G, Rampes H (2003) Adverse effects of khat. A review. Adv Psychiatr Treat 9:456–463CrossRef
go back to reference Efron D, Jarman F, Barker M (1997) Side effects of methylphenidate and dexamphetamine in children with attention deficit disorder: a double-blind, cross-over trial. Pediatrics 100:662–666PubMedCrossRef Efron D, Jarman F, Barker M (1997) Side effects of methylphenidate and dexamphetamine in children with attention deficit disorder: a double-blind, cross-over trial. Pediatrics 100:662–666PubMedCrossRef
go back to reference Eisch AJ, Harburg GC (2006) Opiates, psychostimulants, and adult hippocampal neurogenesis: insights for addiction and Stem Cell Biology. Hippocampus 16:271–286PubMedCrossRef Eisch AJ, Harburg GC (2006) Opiates, psychostimulants, and adult hippocampal neurogenesis: insights for addiction and Stem Cell Biology. Hippocampus 16:271–286PubMedCrossRef
go back to reference Eisenberg MS, Maher TJ, Silverman HI (1987) A comparison of the effects of phenylpropanolamine, d-amphetamine and d-norpseudoephedrine on open-field locomotion and food intake in the rat. Appetite 9:31–37PubMedCrossRef Eisenberg MS, Maher TJ, Silverman HI (1987) A comparison of the effects of phenylpropanolamine, d-amphetamine and d-norpseudoephedrine on open-field locomotion and food intake in the rat. Appetite 9:31–37PubMedCrossRef
go back to reference Fairbanks LA, Jorgensen MJ, Huff A, Blau K, Hung YY, Mann JJ (2004) Adolescent impulsivity predicts adult dominance attainment for male vervet monkeys. Am J Primatol 64:1–17PubMedCrossRef Fairbanks LA, Jorgensen MJ, Huff A, Blau K, Hung YY, Mann JJ (2004) Adolescent impulsivity predicts adult dominance attainment for male vervet monkeys. Am J Primatol 64:1–17PubMedCrossRef
go back to reference Foltin RW, Woolverton WL, Schuster CR (1983) Effects of psychomotor stimulants alone and in pairs, on milk drinking in the rat after intraperitoneal and intragastric administration. J Pharmacol Exp Ther 226:411–418PubMed Foltin RW, Woolverton WL, Schuster CR (1983) Effects of psychomotor stimulants alone and in pairs, on milk drinking in the rat after intraperitoneal and intragastric administration. J Pharmacol Exp Ther 226:411–418PubMed
go back to reference Goldman-Rakic PS, Lidow MS, Gallager DW (1990) Overlap of dopaminergic adrenergic and serotonergic receptors and complementarity of their subtypes in primate prefrontal cortex. J Neurosci 10:2125–2138PubMed Goldman-Rakic PS, Lidow MS, Gallager DW (1990) Overlap of dopaminergic adrenergic and serotonergic receptors and complementarity of their subtypes in primate prefrontal cortex. J Neurosci 10:2125–2138PubMed
go back to reference Gordon TL, Meehan SM, Schechter MD (1993) Differential effects of Nicotine but not cathinone on motor activity of P and NP rats. Biochem Behav 44:657–659CrossRef Gordon TL, Meehan SM, Schechter MD (1993) Differential effects of Nicotine but not cathinone on motor activity of P and NP rats. Biochem Behav 44:657–659CrossRef
go back to reference Goudie AJ (1985) Comparative effects of cathinone and amphetamine on fixed interval operant responding: a rate-dependency analysis. Pharmacol Biochem Behav 23:355–365PubMedCrossRef Goudie AJ (1985) Comparative effects of cathinone and amphetamine on fixed interval operant responding: a rate-dependency analysis. Pharmacol Biochem Behav 23:355–365PubMedCrossRef
go back to reference Isbell LA, Cheney DL, Seyfarth RM (1991) Group fusions and minimum group sizes in vervet monkeys (Cercopithecus aethiops). AM J Primatol 25:57–65CrossRef Isbell LA, Cheney DL, Seyfarth RM (1991) Group fusions and minimum group sizes in vervet monkeys (Cercopithecus aethiops). AM J Primatol 25:57–65CrossRef
go back to reference Ishikawa T, Li Zhu B, Miyashi S, Ishizu H, Maeda H (2007) Increase in clusterin- containing follicles in the adenohypophysis of drug abusers. Int J Legal Med 121:395–402PubMedCrossRef Ishikawa T, Li Zhu B, Miyashi S, Ishizu H, Maeda H (2007) Increase in clusterin- containing follicles in the adenohypophysis of drug abusers. Int J Legal Med 121:395–402PubMedCrossRef
go back to reference James AS, Groman SM, Seu E, Jorgensen M, Fairbanks LA, Jentsch JD (2007) Dimensions of impulsivity are associated with poor spatial working memory performance in monkeys. J Neurosci 27:14358–14364PubMedCrossRef James AS, Groman SM, Seu E, Jorgensen M, Fairbanks LA, Jentsch JD (2007) Dimensions of impulsivity are associated with poor spatial working memory performance in monkeys. J Neurosci 27:14358–14364PubMedCrossRef
go back to reference Jansson T, Kristiansson B, Qirbi A (1988) Effect of khat on maternal food intake, maternal weight gain and fetal growth in the late-pregnant guinea pig. J Ethnopharmacol 23:11–17PubMedCrossRef Jansson T, Kristiansson B, Qirbi A (1988) Effect of khat on maternal food intake, maternal weight gain and fetal growth in the late-pregnant guinea pig. J Ethnopharmacol 23:11–17PubMedCrossRef
go back to reference Kalix P (1983) Mechanism of action of (−) cathinone, a new alkaloid from khat leaves. Alcohol Alcohol 18:301–303 Kalix P (1983) Mechanism of action of (−) cathinone, a new alkaloid from khat leaves. Alcohol Alcohol 18:301–303
go back to reference Kalix P (1984) Effect of the alkaloid (−)-cathinone on the release of radioactivity from rat striatal tissue prelabelled with 3H-serotonin. Neuropsychobiology 12:127–129PubMedCrossRef Kalix P (1984) Effect of the alkaloid (−)-cathinone on the release of radioactivity from rat striatal tissue prelabelled with 3H-serotonin. Neuropsychobiology 12:127–129PubMedCrossRef
go back to reference Kalix P, Braenden O (1985) Pharmacological aspects of the chewing of khat leaves. Pharmacol Rev 37:149–164PubMed Kalix P, Braenden O (1985) Pharmacological aspects of the chewing of khat leaves. Pharmacol Rev 37:149–164PubMed
go back to reference Kimani ST, Nyongesa AW (2008) Effects of single daily khat (Catha edulis) extract on spatial learning and memory in CBA mice. Behav Brain Res 195:192–197PubMedCrossRef Kimani ST, Nyongesa AW (2008) Effects of single daily khat (Catha edulis) extract on spatial learning and memory in CBA mice. Behav Brain Res 195:192–197PubMedCrossRef
go back to reference Lee MM (1995) The identification of cathinone in khat (Catha edulis): a time study. J Forensic Sci 40:116–121 Lee MM (1995) The identification of cathinone in khat (Catha edulis): a time study. J Forensic Sci 40:116–121
go back to reference Marais L, Daniels W, Brand L, Viljoen F, Hugo C, Stein DJ (2006) Psychopharmacology of maternal separation anxiety in vervet monkeys. Metab Brain Dis 21:201–210PubMedCrossRef Marais L, Daniels W, Brand L, Viljoen F, Hugo C, Stein DJ (2006) Psychopharmacology of maternal separation anxiety in vervet monkeys. Metab Brain Dis 21:201–210PubMedCrossRef
go back to reference Martin P, Bateson P (1993) Measuring behaviour: an introductory Guide. Cambridge University Press, CambridgeCrossRef Martin P, Bateson P (1993) Measuring behaviour: an introductory Guide. Cambridge University Press, CambridgeCrossRef
go back to reference Melega WP, Jorgensen MJ, Lacan G, Way BM, Pham J, Morton G, Cho AK, Fairbanks LA (2008) Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioural profiles. Neuropsychopharmacology 33:1441–1452PubMedCrossRef Melega WP, Jorgensen MJ, Lacan G, Way BM, Pham J, Morton G, Cho AK, Fairbanks LA (2008) Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioural profiles. Neuropsychopharmacology 33:1441–1452PubMedCrossRef
go back to reference Mohammed A, Engidawork E (2011) Reproductive parameters are differentially altered following subchronic administration of Catha edulis Forsk (Khat) extract and cathinone in male rats. J Ethnopharmacol 134:977–983PubMedCrossRef Mohammed A, Engidawork E (2011) Reproductive parameters are differentially altered following subchronic administration of Catha edulis Forsk (Khat) extract and cathinone in male rats. J Ethnopharmacol 134:977–983PubMedCrossRef
go back to reference Murray CD, Le Roux CW, Emmanuel AV, Halket JM, Pryborowska AM, Kamm MA, Murray-Lyon IM (2008) The effect of khat (Catha edulis) as an appetite suppressant is independent of ghrelin and PYY secretion. Appetite 51:747–750PubMedCrossRef Murray CD, Le Roux CW, Emmanuel AV, Halket JM, Pryborowska AM, Kamm MA, Murray-Lyon IM (2008) The effect of khat (Catha edulis) as an appetite suppressant is independent of ghrelin and PYY secretion. Appetite 51:747–750PubMedCrossRef
go back to reference Neary NM, Goldstone AP, Bloom SR (2004) Appetite regulation: from the gut to the hypothalamus. Clin Endocrinol 60:153–160CrossRef Neary NM, Goldstone AP, Bloom SR (2004) Appetite regulation: from the gut to the hypothalamus. Clin Endocrinol 60:153–160CrossRef
go back to reference Pehek EA, Schechter MD, Yamamoto BK (1990) Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo. Neuropharmacology 29:1171–1176PubMedCrossRef Pehek EA, Schechter MD, Yamamoto BK (1990) Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo. Neuropharmacology 29:1171–1176PubMedCrossRef
go back to reference Rapkin AJ, Pollack DB, Raleigh MJ, Stone B, McGuire MT (1995) Menstrual cycle and social behaviour in vervet monkeys. Psychoneuroendocrinology 20:289–297PubMedCrossRef Rapkin AJ, Pollack DB, Raleigh MJ, Stone B, McGuire MT (1995) Menstrual cycle and social behaviour in vervet monkeys. Psychoneuroendocrinology 20:289–297PubMedCrossRef
go back to reference Schuster C, Johanson R (1979) Behavioural studies of cathinone in monkeys and rats. In: Problems of Drug Dependence. NIDA Res Monogr 27:324–325 Schuster C, Johanson R (1979) Behavioural studies of cathinone in monkeys and rats. In: Problems of Drug Dependence. NIDA Res Monogr 27:324–325
go back to reference Spoont MR (1992) The modulatory role of serotonin in neural information processing: implications for human psychopathology. Psychol Bull 112:330–350 Spoont MR (1992) The modulatory role of serotonin in neural information processing: implications for human psychopathology. Psychol Bull 112:330–350
go back to reference Sulser F (1989) New perspectives on the molecular pharmacology of affective disorder. Eur Arch Psychiatry Neurol Sci 238:231–239PubMedCrossRef Sulser F (1989) New perspectives on the molecular pharmacology of affective disorder. Eur Arch Psychiatry Neurol Sci 238:231–239PubMedCrossRef
go back to reference Tecott LH, Sun LM, Akana SF, Strack AM, Lowestein DH, Dallman MF, Julius D (1995) Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 374:542–546PubMedCrossRef Tecott LH, Sun LM, Akana SF, Strack AM, Lowestein DH, Dallman MF, Julius D (1995) Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 374:542–546PubMedCrossRef
go back to reference Toennes SM, Kauert GF (2002) Excretion and detection of cathinone, cathine and phenylpropanolamine in urine after khat chewing. Clin Chem 48:1715–1719PubMed Toennes SM, Kauert GF (2002) Excretion and detection of cathinone, cathine and phenylpropanolamine in urine after khat chewing. Clin Chem 48:1715–1719PubMed
go back to reference Toennes SW, Harder S, Schramm M, Neiss C, Kauert GF (2003) Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. Br J Clin Pharmacol 56:125–130PubMedCentralPubMedCrossRef Toennes SW, Harder S, Schramm M, Neiss C, Kauert GF (2003) Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. Br J Clin Pharmacol 56:125–130PubMedCentralPubMedCrossRef
go back to reference Yanagita T (1979) Studies on cathinone: cardiovascular and behavioral effects in rats and self-administration experiments in monkeys. NIDA Res Monogr 2:326–327 Yanagita T (1979) Studies on cathinone: cardiovascular and behavioral effects in rats and self-administration experiments in monkeys. NIDA Res Monogr 2:326–327
go back to reference Zelger J, Carlini E (1980) Anorexigenic effects of two amines obtained from Catha edulis Forsk (khat) in rats. Pharmacol Biochem Behav 12:701–705PubMedCrossRef Zelger J, Carlini E (1980) Anorexigenic effects of two amines obtained from Catha edulis Forsk (khat) in rats. Pharmacol Biochem Behav 12:701–705PubMedCrossRef
go back to reference Zelger J, Schorno H, Carlin E (1980) Behavioural effects of cathinone: an amphetamine obtained from Catha edulis: comparisons with amphetamine, norpseudoephedrine, apomorphine and nomifensine. Bull Narc 32:67–81PubMed Zelger J, Schorno H, Carlin E (1980) Behavioural effects of cathinone: an amphetamine obtained from Catha edulis: comparisons with amphetamine, norpseudoephedrine, apomorphine and nomifensine. Bull Narc 32:67–81PubMed
Metadata
Title
Acute and sub-chronic effects of purified cathinone from khat (Catha edulis) on behavioural profiles in vervet monkeys (Chlorocebus aethiops)
Authors
Albert W. Nyongesa
Jemimah A. Oduma
Motohiro Nakajima
Hesbon O. Odongo
Pius A. Adoyo
Mustafa al’Absi
Publication date
01-06-2014
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 2/2014
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-013-9441-z

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