Central haemodynamics during morphine abstinence in anaesthetized rats.

Central haemodynamics were studied in one group of morphine-dependent rats, and in a non-dependent control group, before and after administration of repeated bolus doses of naloxone. Dependence was induced by s.c. morphine pellet implantations. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO) and mean transit time (MTT) were measured in the conscious state, after induction of chloralose anaesthesia and after the administration of naloxone (0.005, 0.05, 0.5 and 5 mg kg-1 i.v.). Total peripheral resistance (TPR), stroke volume (SV) and central blood volume (CBV) were subsequently calculated. The haemodynamic variables did not differ significantly in the conscious state, except for a lower SV, when compared with the non-dependent control group. However, in response to anaesthesia the dependent rats exhibited a greater fall in MAP, mainly due to a TPR decrease. Naloxone elicited a marked increase in MAP in the morphine-dependent group, which was mainly caused by an increase in TPR. Naloxone induced no significant change compared with the control group in CO and CBV, while SV increased concomitantly with a lowered HR after naloxone in the morphine-dependent group. These results suggest that the withdrawal hypertension during morphine abstinence was mainly explained by an increase in TPR, reflecting an augmented tone of the resistance vessels. The minor changes in CBV indicate that the tone of the venous capacitance vessels was largely unaffected by naloxone-induced morphine abstinence.

[1]  K. Reinhold,et al.  Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats , 1973, Psychopharmacologia.

[2]  R. Russell,et al.  Psychopharmacological evidence for increase in receptor sensitivity following chronic morphine treatment , 2004, Psychopharmacologia.

[3]  K. Starke,et al.  Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[4]  S. Ricksten,et al.  Renal sympathetic nerve activity during morphine abstinence in sino-aortic baroreceptor-denervated rats. , 1988, Acta physiologica Scandinavica.

[5]  M. Delle,et al.  Changes in sympathetic nerve activity during morphine abstinence in the rat. , 1987, Acta physiologica Scandinavica.

[6]  M. E. Lewis,et al.  Anatomy of the CNS opioid systems , 1985, Trends in Neurosciences.

[7]  J. Buccafusco,et al.  Dorsal root lesions block the expression of morphine withdrawal elicited from the rat spinal cord , 1985, Neuroscience Letters.

[8]  J. Buccafusco,et al.  Supraspinal and spinal mediation of naloxone-induced morphine withdrawal in rats , 1985, Brain Research.

[9]  J. Buccafusco,et al.  A comparison of the inhibitory effects of clonidine and guanfacine on the behavioral and autonomic components of morphine withdrawal in rats. , 1984, Life sciences.

[10]  J. Krystal,et al.  Multiple mechanisms of withdrawal from opioid drugs. , 1984, Annual review of neuroscience.

[11]  A. Faden,et al.  Opiate receptors and cardiovascular control in conscious SHR and WKY rats. , 1983, Hypertension.

[12]  J. Buccafusco.  Cardiovascular changes during morphine withdrawal in the rat: Effects of clonidine , 1983, Pharmacology Biochemistry and Behavior.

[13]  A. Faden,et al.  Differential cardiovascular effects of μ, δ and κ opiate agonists at discrete hypothalamic sites in the anesthetized rat , 1982 .

[14]  J. Holaday.  Cardiorespiratory effects of μ and δ opiate agonists following third or fourth ventricular injections , 1982, Peptides.

[15]  S. Ricksten,et al.  Peripheral and central vascular compliances in conscious normotensive and spontaneously hypertensive rats. , 1981, Acta physiologica Scandinavica.

[16]  N. Appel,et al.  β-Endorphin-induced increases in plasma epinephrine, norepinephrine and dopamine in rats: inhibition of adrenomedullary response by intracerebral somatostatin , 1981, Brain Research.

[17]  S. Ricksten,et al.  Reflex inhibition of sympathetic activity during volume load in awake normotensive and spontaneously hypertensive rats. , 1980, Acta physiologica Scandinavica.

[18]  M. Laubie,et al.  Vagal bradycardia produced by microinjections of morphine-like drugs into the nucleus ambiguus in anaesthetized dogs. , 1979, European journal of pharmacology.

[19]  M. Kuhar,et al.  Autoradiographic localization of opiate receptors in rat brain. II. The brain stem , 1977, Brain Research.

[20]  T. Hökfelt,et al.  Immunohistochemical studies using antibodies to leucine-enkephalin: Initial observations on the nervous system of the rat , 1976, Neuroscience.

[21]  B. Oberg,et al.  Circulatory responses to stimulation of left ventricular receptors in the cat. , 1973, Acta physiologica Scandinavica.

[22]  T. Cicero,et al.  Morphine pellet implantation in rats: quantitative assessment of tolerance and dependence. , 1973, The Journal of pharmacology and experimental therapeutics.

[23]  G. Henderson,et al.  A new example of a morphine‐sensitive neuro‐effector junction: Adrenergic transmission in the mouse vas deferens , 1997, British journal of pharmacology.

[24]  G. Henderson,et al.  The variation of noradrenaline output with frequency of nerve stimulation and the effect of morphine on the cat nictitating membrane and on the guinea-pig myenteric plexus. , 1972, British journal of pharmacology.

[25]  R. D. Gibson,et al.  Formulation of a morphine implantation pellet suitable for tolerance-physical dependence studies in mice. , 1970, Journal of pharmaceutical sciences.

[26]  H. Collier,et al.  Supersensitivity and Dependence , 1968, Nature.

[27]  C. Himmelsbach.  STUDIES ON THE RELATION OF DRUG ADDICTION TO THE AUTONOMIC NERVOUS SYSTEM: RESULTS OF COLD PRESSOR TESTS , 1941 .