Purpose: Methamphetamine (METH) blocks and reverses monoamine transporters and its administration evokes behavioural changes associated with frontal brain regions. METH also evokes autonomic effects. We have shown that disinhibition of the medial prefrontal cortex (mPFC) changes cardiorespiratory and metabolic function. We sought to determine whether alterations in monoamine concentrations in the mPFC and nucleus accumbens (NAc) mediate changes in cardiorespiratory and metabolic function. Methods: Electrophysiological experiments were performed in urethane-anaesthetised, artificially ventilated, vagotomised, male Sprague-Dawley rats. Microinjections of METH (35, 105, 335 nmol), dopamine hydrochloride (DA 10, 50 ,150, 475 nmol) or L-norepinephrine (NA 10, 50, 150 nmol) were made into the infralimbic cortex of the mPFC and NAc. Changes were recorded in iBAT, heart rate (HR), expired CO2, phrenic nerve amplitude and frequency (PNamp and PNf), mean arterial pressure (MAP), splanchnic and lumbar sympathetic nerve activity. Results: METH in PFC evoked respiratory depression at low doses but increased all parameters at high doses. DA evoked increases in thermogenic and metabolic outflows (iBAT;2.2±0.3 deg C, HR;21±4bpm and expired CO2;0.67±0.11% (n=5)) and in respiratory function (PNf;11±1bpm, and, PNamp;137±15% (n=5)) with little change in other parameters only at the highest dose with only respiratory depression evoked at low doses. In contrast in the PFC NA evoked dose dependent increases in MAP (18±2mmHg, 10ug/kg, n=5), iBAT (0.8±0.15 degC), HR (16±2bpm) and expired CO2 (0.35±0.07%) and respiratory function. Conclusions: In PFC respiratory depressant effects were evoked by low doses of METH and these were mimicked by low doses of DA. The increased cardiovascular, respiratory and metabolic function evoked by METH in PFC was mimicked by NA, although DA may also contribute. Alteration in monoamine levels in frontal brain regions alters cardiorespiratory and metabolic function.