Lateralized attenuation of hypothalamic self-stimulation after injecting histamine synthesis blocker alpha-FMH into...

The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, is the only known source of neuronal histamine. Unilateral lesions in the rostroventral part of this nucleus enhanced ipsihemispheric lateral hypothalamic self-stimulation behavior, suggesting that this region exerts inhibitory control over the neuronal systems related to reward or reinforcement processes. To examine whether the amplification of reinforcing stimulation following lesions of histamine synthesizing neurons is indeed histamine mediated, we blocked histamine synthesis unilaterally by injection of 200 microg alpha-fluoromethylhistidine into the E2 region of the TM, and assessed the effects on electrical self-stimulation behavior in the lateral hypothalamus (LH) of rats. Based on the finding that TM lesions facilitated such self-stimulation behavior, we hypothesized that this treatment would have similar effects. Unexpectedly, there was a sharp decrease in the rate of ipsihemispheric lateral hypothalamic self-stimulation following the injection of alpha-FMH compared to the contralateral hemisphere of treated animals as well as compared to the vehicle group. Response rates were most strikingly attenuated 1 h postinjection, but remained low over the whole 7 days of testing. Opposite behavioral effects of TM lesions and alpha-FMH application have been reported previously, and the effectiveness of alpha-FMH in reducing brain histamine levels is known to differ between brain regions. The fact that the alpha-FMH injection affected self-stimulation only in the ipsilateral hemisphere rules out an interpretation of the results in terms of unspecific effects of the treatment on arousal and other performance variables, and, instead, indicates a functional interaction with a subsystem linked to lateral hypothalamic reinforcement processes.