title: Comparison of noradrenaline, dopamine and serotonin in mediating the tachycardic and thermogenic effects of methamphetamine in the ventral medial prefrontal cortex.
abstract: Methamphetamine (METH) is a psychostimulant that disrupts monoaminergic neurotransmission to evoke profound behavioral and physiological effects. Rapidly distributing to forebrain regions to increase synaptic concentrations of three monoamines (dopamine (DA), serotonin (5-HT) and noradrenaline (NA)), the medial prefrontal cortex (mPFC) is important in METH-altered behavioral and psychological profiles. Activation of the ventral mPFC can modify physiological variables, however, METH-evoked autonomic changes from this region are unknown. Therefore, the aim of this study was to characterize the respiratory, metabolic and cardiovascular effects of microinjection of METH, DA, 5-HT and NA into the ventral mPFC in urethane-anesthetized Sprague-Dawley rats. METH and NA microinjection evoked dose-related increases in heart rate, interscapular brown adipose tissue temperature and expired CO2, a pattern of response characteristic of non-shivering thermogenesis. NA and 5-HT microinjection elicited pressor and depressor responses, respectively, with matching baroreflex adjustments in sympathetic nerve activity while METH and DA evoked no change in vasomotor outflow. Low doses of METH and DA may evoke respiratory depression. These data suggest that METH's actions in the ventral mPFC, likely via adrenergic receptors, evoke non-shivering thermogenesis which may contribute to the increased body temperature and tachycardia seen in those that abuse METH.
authors: The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.
authors: S F
authors: SF
authors: Hassan
authors: The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.
authors: S
authors: S
authors: Zumut
authors: The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.
authors: P G
authors: PG
authors: Burke
authors: The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.
authors: S
authors: S
authors: McMullan
authors: Neuropharmacology Laboratory, Department of Psychology, Macquarie University, NSW 2109, Australia.
authors: J L
authors: JL
authors: Cornish
authors: The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia. Electronic address: ann.goodchild@mq.edu.au.
authors: A K
authors: AK
authors: Goodchild
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D022722:Thermogenesis / Q000187:drug effects*
chemical_list: D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine; D009638:Norepinephrine
keywords: cardiovascular; respiration; thermoregulation