Histamine: Correlative studies in nucleus accumbens

Abstract

The role of histamine as a neurotransmitter has been the subject of considerable controversy. 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 H1 antagonist promethazine was greater than the H2 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 H1 and H2 receptors or cellular disruption reflects the loss of receptor specificity. Physiological studies demonstrated that the H2 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 H1 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 H2 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.

Neurokinin B‐producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat

“…The cell clusters in the rat Acb were first studied in detail by Herkenham et al (1984), although some anatomical reports on the rat Acb nucleus were found in the older literature (Chronister et al, 1982). Herkenham et al (1984) reported that the cell clusters were composed of densely packed medium-sized spiny neurons, were distinguished from the islands of Calleja of much smaller granule cells, and were only poorly innervated by the inputs from the thalamic nuclei or ventral tegmental area.…”

Histamine and the striatum

“…It was thus clear that histamine could regulate some aspects of the striatal circuit but there were still many questions outstanding. These included the potential modulation of the thalamic projection to the striatum, which forms the other major excitatory glutamatergic afferent to the striatum ( Smith et al., 2014 ), and the potential differential modulation of the two main types of striatal MSN (see Table 1 ) Indeed, several in vivo studies of the activity patterns in the striatum came to different conclusions on the effect of histamine on striatal neural activity with both increases ( Sittig and Davidowa, 2001 ) and decreases ( Chronister et al., 1982 ) in neural activity reported upon histamine infusion in vivo . Most likely these conflicting results result from the inherent heterogeneity of striatal neurons.…”

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

“…The accumbens was chosen for several reasons; firstly, substantial levels of histamine have been measured in this regior (Bennett et al, 1983) and more recently, immunohistochemical studies have suggested a histaminergic pathway arising from cell bodies in the posterior hypothalamus and terminating in the accumbens (Steinbusch & Mulder, 1985;Pollard & Schwartz, 1987). Thirdly, histamine agonists have been shown to alter neuronal firing in rabbit accumbens and activation of adenylate cyclase in this region appears to be mediated by both H1and H2-receptors (Chronister et al, 1982). Finally, it is well established that the nucleus accumbens plays an important role in the control of motor activity (Mogenson et al, 1980).…”