Modification of apomorphine hypothermia by drugs affecting brain 5-hydroxytryptamine function

Area of Science:

• Neuropharmacology
• Thermoregulation
• Serotonin Receptor Modulation

Background:

• Apomorphine, a dopamine agonist, induces hypothermia in mice.
• Serotonin (5-HT) is implicated in modulating various physiological processes, including body temperature.
• Understanding the interaction between dopamine and serotonin systems is crucial for deciphering thermoregulatory mechanisms.

Purpose of the Study:

• To investigate the role of serotonin (5-HT) in dopamine-mediated hypothermia.
• To determine how 5-HT receptor antagonists and agonists affect apomorphine-induced hypothermia.
• To explore the potential for tolerance and cross-tolerance between drugs affecting the 5-HT system.

Main Methods:

• Administration of apomorphine to induce hypothermia in mice.
• Pretreatment with various serotonin receptor antagonists (methysergide, cinanserin, brom-LSD) and agonists (quipazine, MK-212, LSD).
• Assessment of body temperature changes following drug administration and manipulation of brain 5-HT levels via p-chlorophenylalanine.

Main Results:

• Serotonin receptor antagonists and brain 5-HT depletion potentiated apomorphine-induced hypothermia.
• Serotonin receptor agonists (quipazine, MK-212, LSD) significantly blocked apomorphine hypothermia.
• Tolerance and cross-tolerance were observed between quipazine and LSD in blocking apomorphine hypothermia.

Conclusions:

• Serotonin (5-HT) plays a significant modulatory role in dopamine (DA)-mediated body temperature regulation.
• Drug-induced alterations in brain 5-HT function predictably modify apomorphine-induced hypothermia.
• The hypothermia-blocking effect of LSD is attributed to its action on hypothalamic 5-HT receptors.