Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

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• 作者：Sinead E. Shortall ; Clare H. Spicer ; Francis J. P. Ebling ; A. Richard Green ; Kevin C. F. Fone and Madeleine V. King
• 刊名：Addiction Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：21
• 期：6
• 页码：1127-1139
• 全文大小：746K
• ISSN：1369-1600

文摘

The psychoactive effects of mephedrone are commonly compared with those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action, users often employ repeated administration to maintain its psychoactive effects. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1 ml/kg, i.p.) or mephedrone HCl (10 mg/kg) at 2 h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (150 µg) or 6-hydroxydopamine (300 µg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (−30 min) with the 5-HT_1A receptor antagonist WAY-100635 (0.5 mg/kg), 5-HT_1B receptor antagonist GR 127935 (3 mg/kg) or the 5-HT₇ receptor antagonist SB-258719 (10 mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing) and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT_1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT_1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT_1B and 5-HT_1A receptors.