Naloxone-precipitated morphine withdrawal evokes phosphorylation of heat shock protein 27 in rat heart through extracellular signal-regulated kinase

Morphine Withdrawal Activates Hypothalamic-Pituitary-Adrenal Axis and Heat Shock Protein 27 in the Left Ventricle: The Role of Extracellular Signal-Regulated Kinase

“…Previous studies have demonstrated that chronic -opioid receptor stimulation decreases muscle sympathetic nerve activity (Kienbaum et al, 2001(Kienbaum et al, , 2002, NA plasma concentration (Kienbaum et al, 2001), dopamine turnover in the heart (Rabadá n et al, 1997), and mean arterial pressure and heart rate (Almela et al, 2011). However, -opioid receptor blockade by naloxone in patients with chronic opioid abuse or jpet.aspetjournals.org morphine-dependent rats unmasks these effects, resulting in markedly increased muscle sympathetic nerve activity, plasma NA concentrations (Peart and Gross, 2006), NA and dopamine turnover (Almela et al, 2008), total tyrosine hydroxylase expression (Almela et al, 2009), and an enhancement in mean arterial pressure and heart rate (Almela et al, 2011), two objective and accurate measurable signs of opioid withdrawal in humans.…”

“…However, -opioid receptor blockade by naloxone in patients with chronic opioid abuse or jpet.aspetjournals.org morphine-dependent rats unmasks these effects, resulting in markedly increased muscle sympathetic nerve activity, plasma NA concentrations (Peart and Gross, 2006), NA and dopamine turnover (Almela et al, 2008), total tyrosine hydroxylase expression (Almela et al, 2009), and an enhancement in mean arterial pressure and heart rate (Almela et al, 2011), two objective and accurate measurable signs of opioid withdrawal in humans. The present results demonstrated that withdrawal caused a decrease in myocardial NA levels and increases in myocardial NMN (extraneuronal NA metabolite generated by COMT), in parallel with an increased expression of two isoforms of COMT (MB-COMT and S-COMT), suggesting that both forms of COMT are implicated in the degradation of NA.…”

“…Altogether, these results suggest that neurochemical and/or neurohormonal and neural stimulatory factors other than adrenocorticotropin might be responsible for adrenal hyperactivity observed during morphine withdrawal, so the separation of adrenocorticotropin and corticosteroid secretion could have clinical relevance on endocrine stress regulation. Because the repeated exposure to morphine and its withdrawal induces profound and severe stress reactions that are also evidenced by overexpression of Hsp27 (Almela et al, 2011;Houshyar et al, 2001aHoushyar et al, , 2001bSharma, 2004;Sharma et al, 2004) we have evaluated Hsp27 expression and activation in the left ventricle. Like previous data (Almela et al, 2011), the present investigation shows that chronic morphine treatment and its withdrawal are associated with an increase of Hsp27 expression.…”

“…In rats activation of the HPA axis has been observed with agonists of the three types of opioid receptors when given peripherally and centrally (Haracz et al, 1981;Pfeiffer et al, 1985;Iyengar et al, 1987), and it has been described that, like stressors, morphine withdrawal increases heart rate (Almela et al, 2011) and activates the HPA axis in rats, which results in the neuronal activation of stress-related neurosecretory neurons in the parvocellular neurons of the hypothalamic paraventricular nucleus (PVN), an increase in CRF transcription, and boosts of adrenocorticotropin and corticosterone secretion (Laorden et al, 2002;Cleck and Blendy, 2008;Nú ñ ez et al, 2009). Furthermore, the profound cellular stress induced by chronic morphine treatment and withdrawal is also evidenced by the overexpression of heat shock proteins (Hsps) (Kas, 1987;Sharma and Ali, 2006).…”

Pathways Involved in the Cardiac Adaptive Changes Observed During Morphine Withdrawal

“…ERK signalling pathway could be important as regulator of cardiac function ) and neuronal plasticity (Adams et al, 2002). Recently, several studies have shown that this pathway contributes to naloxone-precipitated withdrawal in morphine dependent rats (Ren et al, 2004;Almela et al, 2007Almela et al, , 2008Almela et al, , 2011.…”