Histopathological Evaluation of Brain Edema Fluid Dynamics in Relation to Tissue Repair in Rats with Cryogenic Cortical Lesion

The role of histamine as a neurotransmitter has been the subject of considerable controvery. Recent evidence suggests it to be involved in such complex activities as arousal and affect. The purpose of the present study is to examine the possible source, function, and pharmacology of histamine in the nucleus accumbens, an area of the brain also implicated in complex activities such as affect. The anatomical studies suggest that the most probable source of the histamine in nucleus accumbens is the complex region lateral to the mammillary nuclei. These areas are the intercalated nucleus and the tuberomammillary nucleus (nuclei gemini hypothalami). To a lesser degree, the supramammillary complex may also contribute histamine‐containing axons to the accumbens area. Adenylate cyclase in the rabbit nucleus accumbens displayed activation in response to histamine agonists (histamine, 2‐Me‐histamine, and 4‐Me‐histamine). The action of the H 1 antagonist promethazine was greater than the H 2 antagonist metiamide in reducing enzyme activation by histamine and 2‐Me‐histamine. In contrast, metiamide was more potent than promethazine toward antagonism of the action of 4‐Me‐histamine. However, no additive effects were noted when agonists were added in combination. Based upon these data, it is suggested that activation of adenylate cyclase in the rabbit nucleus accumbens is mediated in part by mixed H 1 and H 2 receptors or cellular disruption reflects the loss of receptor specificity. Physiological studies demonstrated that the H 2 agonist 4‐Me‐histamine had an inhibitory effect on the activity of neurons driven by stimulation of the fimbria. The magnitude of the effect was frequency dependent. The H 1 agonist 2‐Me‐histamine had no significant effect. Iontophoretic application of 4‐Me‐histamine had minimal effect upon low frequency volleys (0.5 Hz) but had a pronounced effect upon higher frequency volleys (6.0 Hz). These effects were antagonized by metiamide. Iontophoretic application of metiamide alone produced an effect only upon the P component of the field response, which is also bicuculline sensitive. Bicuculline coadministration was also effective in antagonizing the 4‐Me‐histamine effect. The physiological data suggest that histamine works through H 2 receptors in nucleus accumbens, perhaps by potentiating the effects of gamma‐aminobutyric acid (GABA). Thus histamine in nucleus accumbens appears to function as a modulatory substance whose effect is dependent upon the activity of other transmitter and afferent systems.