Related Experiment Video
Updated: Jun 19, 2026

04:11
A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Morphine induces conditioned place preference behavior in histidine decarboxylase knockout mice
Ying-xia Gong1, Wei-ping Zhang, Wen-ting Shou
1Department of Pharmacology, Yunyang Medical College, Shiyan, China.
Neuroscience Letters
|November 3, 2009
Summary
Endogenous histamine inhibits the development of morphine reward-seeking behavior but not its extinction. Histamine deficiency in mice enhanced morphine reward and reduced withdrawal symptoms, suggesting a role in modulating dopamine.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Histamine is known to inhibit morphine-induced reward-seeking behavior.
- Endogenous histamine's role in morphine reward and withdrawal remains unclear.
Purpose of the Study:
- To investigate the role of endogenous histamine in morphine-induced reward-seeking behavior.
- To examine the effect of histamine deficiency on morphine reward and withdrawal using genetically modified mice.
Main Methods:
- Utilized histidine decarboxylase gene knockout (HDC-KO) mice and wild-type (WT) littermates.
- Assessed morphine-induced conditioned place preference (CPP) and its extinction.
- Measured dopamine levels in the ventral tegmental area (VTA) and nucleus accumbens (NAc).
- Evaluated naloxone-precipitated withdrawal jumping behavior.
Main Results:
- HDC-KO mice exhibited stronger morphine-induced CPP compared to WT mice.
- Morphine increased dopamine levels in the VTA and NAc, with a more pronounced effect in HDC-KO mice.
- CPP extinction was similar in both genotypes.
- HDC-KO mice showed significantly reduced naloxone-precipitated withdrawal jumping.
Conclusions:
- Endogenous histamine inhibits the development of morphine-induced CPP, but not its extinction.
- Histamine deficiency enhances morphine reward and reduces withdrawal severity, likely via modulation of dopaminergic activity.
- These findings highlight histamine as a potential target for managing opioid reward and withdrawal.
Related Concept Videos
Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...

