Related Experiment Video
Updated: Aug 15, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Modification of different morphine actions by 6-hydroxydopamine and 6-hydroxydopamine plus desmethylimipramine
Abstract:
After intracisternal 6-hydroxydopamine (6-OHDA) in mice, brain noradrenaline (NA) and dopamine (DA) are diminished, although the reduction of NA is more pronounced. Intracisternal injection of 6-OHDA in desmethylimipramine (DMI)-pretreated animals strengthens the depletion of DA while NA is partly protected. The concentration of 5-hydroxytryptamine (5-HT) is not influenced by 6-OHDA or 6-OHDA + DMI. Chronic morphine treatment to some extent enhances reduced NA and DA levels after 6-OHDA, but the decreased central catecholamine (CA) content after 6-OHDA + DMI is not raised. Morphine analgesia is highly attenuated in 6-OHDA and 6-OHDA + DMI mice. The reduction occurs in non-tolerant as well as in tolerant animals. The acute effect of morphine on body temperature is abolished with 6-OHDA, but not with 6-OHDA + DMI, whereas the interaction of central CA in morphine-induced running shows distinctly marked reduction with 6-OHDA + DMI, but not with 6-OHDA. Acute toxicity is enhanced by 6-OHDA + DMI whereas the development of tolerance against the toxicity of morphine is diminished by 6-OHDA. Lack of CA in the brain decreases sensitivity against naloxone withdrawal in acute as well as in chronic experiments.
Related Concept Videos
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...
Drugs Affecting Neurotransmitter Synthesis
Opioid Receptors: Overview
Analgesia and Pain Management
Opioid Analgesics: Morphine and Other Natural Cogeners
Opioid Analgesics: Synthetic and Semisynthetic Opioids

