A telemetric examination of cardiovascular function during the development of, and recovery from, opiate dependence in rats Gavan P. McNally a, ⁎ , Pascal Carrive b a School of Psychology, The University of New South Wales, Sydney, 2052, Australia b School of Medical Sciences, The University of New South Wales, Australia Received 23 September 2005; received in revised form 10 January 2006; accepted 7 March 2006 Abstract Rats were subject to daily injections of morphine or saline and were then allowed to spontaneously withdraw from morphine for 4 days. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded continuously, via radiotelemetry, during the development of, and recovery from, opiate dependence. Injections of morphine produced pronounced and prolonged increases in MAP and HR which increased as morphine dose increased. There were also significant increases in MAP during the 19–23 h period after each morphine injection indicating the presence of withdrawal. Spontaneous withdrawal from morphine was associated with a pronounced (20% increase from baseline) and prolonged (72 h) increase in MAP. MAP returned to baseline levels 72–96 h after last morphine exposure. These results show that intermittent injections of morphine, and spontaneous withdrawal from these injections, are associated with profound alterations in cardiovascular function and confirm the usefulness of radiotelemetry for studying opiate dependence. © 2006 Elsevier Inc. All rights reserved. Keywords: Morphine; Withdrawal; Cardiovascular function 1. Introduction Prolonged administrations of opiates produce the develop- ment of tolerance and withdrawal. The withdrawal syndrome from opiates in humans includes cognitive (e.g., drug craving), affective (e.g., anxiety), and behavioural (e.g., twitches) signs [16]. Changes in autonomic function are also key indicators of opiate withdrawal. These can include cardiovascular alterations (e.g., heart rate and blood pressure), changes in respiration, and changes in thermoregulation [6]. Despite the important place of autonomic changes in the opiate withdrawal syndrome, there have been few investigations into autonomic function during dependence and withdrawal from opiates using animal models [1,2,4,17]. Chan et al. [4] implanted rats with radiotelemetry probes to continuously monitor blood pressure and heart rate in the freely moving animal. They also implanted rats with minipumps to continu- ously deliver morphine. They showed that delivery of morphine produced small increases in blood pressure which displayed tolerance across prolonged exposures. Precipitation of with- drawal via removal of the minipumps also resulted in a small but significant increase in blood pressure as well as heart rate. Similar increases in blood pressure have been reported in rats following antagonist-precipitated withdrawal [1,2,17] and in humans during spontaneous [10,11,14] and antagonist-precip- itated [6] withdrawal. The relative lack of research into the autonomic correlates of opiate dependence and withdrawal in animals is surprising because investigations into the patterns of neural activation associated with opiate withdrawal consistently identify pronounced activation of central autonomic circuits. For example, it is well documented that withdrawal from opiates induces immediate early gene expression in structures such as the nucleus of the solitary tract, rostral and caudal ventrolateral medulla, A5 catecholaminergic group, parabra- chial nuclei, locus coeruleus, paraventricular nucleus of the hypothalamus, amygdala and thoracic spinal cord [8,9,13,15, 18,19,22,23], all of which play critical roles in regulating autonomic function. Although past studies have identified robust changes in autonomic function during opiate withdrawal, they have also left unanswered a number of important questions. First, the time Physiology & Behavior 88 (2006) 55 – 60 ⁎ Corresponding author. Tel.: +61 2 93853044; fax: +61 2 93853641. E-mail address: g.mcnally@unsw.edu.au (G.P. McNally). 0031-9384/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2006.03.007