Histaminergic drugs in the rat caudate nucleus: effects on learned helplessness.

The effect of pharmacological manipulation of histaminergic receptors in the caudate nucleus (CN) has been examined in rats previously submitted to inescapable electric shock to produce learned helplessness (LH). Histamine H1 agonist 2-tiazolylethyl amine (TEA) microinjection produced protective effects, preventing the activity and cognitive loss typical in LH. Injection of the H1 antagonist astemizole (AZ) produced effects symmetrical to those produced by TEA, further reducing activity and impairing cognitive functions. The histamine H2 agonist 4-methyl-histamine (4MH) produced a shift on the side preference for rotation that interfered in the learning tests and obscured the effects of this drug on LH. Injection of the H2 antagonist cymetidine (CYM) caused LH-like effects in control animals. Thus, brain histamine seems to play a relevant role in the control of motor and cognitive functions of the CN.