Biphasic effects of intra‐accumbens histamine administration on spontaneous motor activity in the rat; a role for central histamine receptors

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Abstract
The effect of intra‐accumbens injection of histamine and related compounds on the spontaneous motor activity of the rat has been investigated. Microinjections of histamine (1–200μg) induced dose‐dependent, biphasic changes in rat activity consisting of an initial brief hypoactivity response followed by a marked hyperactivity phase. The histamine metabolite, n‐tele‐methylhistamine was without effect. Pretreatment with the H1‐receptor antagonist mepyramine (10 μg) blocked the hypoactivity response and markedly attenuated histamine‐induced hyperactivity. In contrast, pretreatment with the H2‐receptor antagonist SKF93479 had no effect on histamine‐induced behaviour. Microinjection of the H1‐receptor agonist 2‐thiazolylethylamine induced a marked hyperactivity response, but unlike the response to histamine, there was no initial hypoactivity. The H2‐receptor agonist dimaprit had no apparent behavioural effects following intra‐accumbens injection. Intra‐accumbens injection of the non‐selective histamine agonists nα‐methylhistamine or nα, nα‐dimethylhistamine induced both marked hypoactivity and hyperactivity responses which were comparable with the effects of histamine. The present results demonstrate a histamine, H1‐receptor‐mediated arousal in the nucleus accumbens which follows transitory hypoactivity, possibly due to activation of presynaptic H3‐receptors.