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Involvement of histaminergic mechanisms in the cataleptogenic effect of morphine in mice
Abstract:
Intraperitoneally administered morphine induced catalepsy in mice. Morphine pretreatment however, failed to antagonize apomorphine-induced cage climbing behaviour thereby ruling out the possibility of its possessing DA receptor blocking activity. Pretreatment with L-histidine, a precursor of histamine, and atropine, potentiated the cataleptic effect of morphine whilst pretreatment with chlorcyclizine, an H1 receptor blocker, and naloxone, a morphine antagonist, antagonized morphine-catalepsy. Pretreatment with metiamide, an H2 receptor blocker, and methysergide, a 5-HT antagonist, did not significantly alter the cataleptic effect of morphine. The results with L-histidine and chlorcyclizine suggest an involvement of central histaminergic mechanisms in the cataleptogenic effect of morphine in mice. Further, as the cataleptic effect of morphine was also antagonized by naloxone it appears that the interaction of morphine with the central histaminergic mechanisms is mediated through specific opiate receptors.
Insights
Morphine-induced catalepsy in mice involves histamine pathways, not dopamine receptors. Histamine precursor L-histidine and H1 blocker chlorcyclizine potentiated and antagonized morphine catalepsy, respectively, suggesting central histaminergic involvement.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Morphine is a potent opioid analgesic.
- Opioid-induced side effects, like catalepsy, require understanding of underlying mechanisms.
- Histaminergic and dopaminergic systems are implicated in motor control and drug effects.
Purpose of the Study:
- To investigate the role of central histaminergic and dopaminergic systems in morphine-induced catalepsy in mice.
- To elucidate the receptor interactions involved in morphine's cataleptogenic effects.
Main Methods:
- Administration of morphine intraperitoneally to induce catalepsy in mice.
- Pretreatment with various agents including L-histidine, atropine, chlorcyclizine (H1 blocker), metiamide (H2 blocker), methysergide (5-HT antagonist), and naloxone (morphine antagonist).
- Assessment of the effects of these pretreatments on morphine-induced catalepsy and apomorphine-induced climbing behavior.
Main Results:
- Morphine induced catalepsy, but did not block apomorphine-induced climbing, ruling out direct dopamine receptor blockade.
- L-histidine and atropine potentiated morphine catalepsy.
- Chlorcyclizine and naloxone antagonized morphine catalepsy.
- Metiamide and methysergide had no significant effect on morphine catalepsy.
Conclusions:
- Central histaminergic mechanisms are involved in morphine-induced catalepsy.
- The interaction of morphine with histaminergic systems appears to be mediated via specific opiate receptors, as evidenced by naloxone antagonism.