Related Experiment Video
Updated: Aug 16, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Changes in catecholaminergic pathways innervating paraventricular nucleus and pituitary-adrenal axis response during
M L Laorden1, G Fuertes, A González-Cuello
1Department of Physiology and Pharmacology, Unit of Pharmacology, University School of Medicine, Murcia, Spain.
Abstract:
We have previously shown an enhanced activity of the pituitary-adrenal response in rats dependent on morphine, which occurs concomitantly with an increase in the activity of catecholaminergic terminals in the hypothalamic paraventricular nucleus (PVN). The present study examined the possible role of noradrenergic system in the regulation of opioid withdrawal-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis activity. Rats were given morphine by s.c. implantation of morphine pellets for 7 days. On the seventh day, morphine withdrawal was induced by s.c. administration of naloxone (1 mg/kg), rats were sacrificed 30 min later, and changes in noradrenaline (NA) turnover (estimated by the 3-methoxy-4-hydroxyphenylethylen glycol/NA ratio) and in dopamine turnover (estimated by the 3,4-dihydroxyphenylacetic acid/dopamine ratio) in the PVN (HPLC with electrochemical detection) and in plasma corticosterone levels were determined. We found a parallelism between the behavioral signs of withdrawal, an increased activity of noradrenergic and dopaminergic terminals in the PVN, and the hypersecretion of the HPA axis. Pretreatment with alpha(1)- or alpha(2)-adrenoceptor antagonists prazosin or yohimbine, respectively, 15 min before naloxone administration significantly prevented the withdrawal-induced corticosterone hypersecretion and attenuated the behavioral signs of morphine withdrawal. In addition, biochemical analysis indicated that both prazosin and yohimbine completely abolished the withdrawal-induced increase in NA turnover in the PVN. In contrast, neither prazosin nor yohimbine modified the hyperactivity of dopaminergic terminals in the PVN during withdrawal. Collectively, these data suggest that the secretory activity in the HPA axis after morphine withdrawal results from an increase in noradrenergic activity that is dependent on alpha(1)- and alpha(2)-adrenoceptor activation. Activation of dopaminergic pathways might not contribute to the neuroendocrine response during withdrawal.
Related Concept Videos
Adrenergic Receptors (Adrenoceptors): Classification
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic...
Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Opioid Receptors: Overview
Analgesia and Pain Management

