Biphasic effects of intra-accumbens histamine administration on spontaneous motor activity in the rat; a role for central histamine receptors.
1. The effect of intra-accumbens injection of histamine and related compounds on the spontaneous motor activity of the rat has been investigated. 2. Microinjections of histamine (1-200 micrograms) 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. 3. Pretreatment with the H1-receptor antagonist mepyramine (10 micrograms) 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. 4. 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. 5. Intra-accumbens injection of the non-selective histamine agonists n alpha-methylhistamine or n alpha, n alpha-dimethylhistamine induced both marked hypoactivity and hyperactivity responses which were comparable with the effects of histamine. 6. 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.
Bristow
L J
LJ
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
Bennett
G W
GW
D000818:Animals; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology
D008761:Methylhistamines; D011968:Receptors, Histamine; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; D006632:Histamine; D011738:Pyrilamine; C020404:tele-methylhistamine