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Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes
Author(s) -
Hassan Sarah F.,
Wearne Travis A.,
Cornish Jennifer L.,
Goodchild Ann K.
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp271257
Subject(s) - meth , medicine , methamphetamine , hyperthermia , thermogenesis , reflex , anesthesia , cardiorespiratory fitness , heart rate , respiratory system , blood pressure , pharmacology , adipose tissue , chemistry , monomer , organic chemistry , acrylate , polymer
Key points Methamphetamine (METH) abuse is escalating worldwide, with the most common cause of death resulting from cardiovascular failure and hyperthermia; however, the underlying physiological mechanisms are poorly understood. Systemic administration of METH in anaesthetised rats reduced the effectiveness of some protective cardiorespiratory reflexes, increased central respiratory activity independently of metabolic function, and increased heart rate, metabolism and respiration in a pattern indicating that non‐shivering thermogenesis contributes to the well‐described hyperthermia. In animals that showed METH‐induced behavioural sensitisation following chronic METH treatment, no changes were evident in baseline cardiovascular, respiratory and metabolic measures and the METH‐evoked effects in these parameters were similar to those seen in saline‐treated or drug naïve animals. Physiological effects evoked by METH were retained but were neither facilitated nor depressed following chronic treatment with METH. These data highlight and identify potential mechanisms for targeted intervention in patients vulnerable to METH overdose.Abstract Methamphetamine (METH) is known to promote cardiovascular failure or life‐threatening hyperthermia; however, there is still limited understanding of the mechanisms responsible for evoking the physiological changes. In this study, we systematically determined the effects on both autonomic and respiratory outflows, as well as reflex function, following acute and repeated administration of METH, which enhances behavioural responses. Arterial pressure, heart rate, phrenic nerve discharge amplitude and frequency, lumbar and splanchnic sympathetic nerve discharge, interscapular brown adipose tissue and core temperatures, and expired CO 2 were measured in urethane‐anaesthetised male Sprague‐Dawley rats. Novel findings include potent increases in central inspiratory drive and frequency that are not dependent on METH‐evoked increases in expired CO 2 levels. Increases in non‐shivering thermogenesis correlate with well‐described increases in body temperature and heart rate. Unexpectedly, METH evoked minor effects on both sympathetic outflows and mean arterial pressure. METH modified cardiorespiratory reflex function in response to hypoxia, hypercapnia and baroreceptor unloading. Chronically METH‐treated rats failed to exhibit changes in baseline sympathetic, cardiovascular, respiratory and metabolic parameters. The tonic and reflex cardiovascular, respiratory and metabolic responses to METH challenge were similar to those seen in saline‐treated and drug naive animals. Overall, these findings describe independent and compound associations between physiological systems evoked by METH and serve to highlight that a single dose of METH can significantly impact basic homeostatic systems and protective functions. These effects of METH persist even following chronic METH treatment.