Methamphetamine and brain histamine: a study using histamine-related gene knockout mice

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Central histamine (HA) neurons in the posterior hypothalamus regulate diverse physiological functions.
• The histaminergic system's role in methamphetamine (METH) behavioral effects requires elucidation.

Purpose of the Study:

• To investigate the influence of the brain histaminergic neuron system on METH-induced behavioral responses.
• To determine the specific roles of histamine H1 and H2 receptors in METH's action.

Main Methods:

• Administration of METH to gene knockout mice (L-histidine decarboxylase [HDC]-, histamine H1 receptor-, H2 receptor-deficient, and double H1/H2 receptor-deficient) and wild-type controls.
• Measurement of locomotor activity following METH administration.
• Neurochemical analysis of monoamine and amino acid levels in HDC-gene knockout and wild-type mice brains after acute METH exposure.

Main Results:

• METH-induced locomotor hyperactivity was significantly enhanced in HDC-gene knockout and H1/H2 receptor-gene double knockout mice compared to wild-type mice.
• The development of behavioral sensitization to METH was also facilitated in these knockout models.
• Neurochemical data suggested that brain histamine exerts an inhibitory effect on METH action via both H1 and H2 receptors.

Conclusions:

• Brain histamine acts as an inhibitor of METH's behavioral effects, mediated through both histamine H1 and H2 receptors.
• The GABAergic neuron system appears to be involved in the inhibitory mechanism of brain histamine on METH action.