Distinct and interactive effects of d-amphetamine and haloperidol on levels of neurotensin and its mRNA in subterritories in the dorsal and ventral striatum of the rat

Abstract

Striatal tissue concentrations of neurotensin, expression of neurotensin/neuromedin N (NT/N) mRNA, and numbers of neurotensin-immunoreactive neurons are increased by d-amphetamine (amph), which stimulates dopamine release in the striatum, and haloperidol (hal), a dopamine receptor antagonist with high affinity for D2-like receptors. The possibility that the effects of these drugs involve distinct subpopulations of striatal neurons was addressed in this study, in which the relative numbers and distributions of striatal neuron profiles containing neurotensin immunoreactivity and/or NT/N mRNA were compared following administrations of hal, amph, hal and amph co-administered, and vehicle. Fourteen striatal subterritories in caudate-putamen, nucleus accumbens, and olfactory tubercle were evaluated. Amph produced increases in the expression of neurotensin preferentially in the ventromedial and caudodorsal subterritories of the caudate-putamen, the rostrobasal cell cluster and lateral shell of the nucleus accumbens, and the olfactory tubercle. Haloperidol produced increased neurotensin expression in much of dorsal and ventral striatum, most prominently in the rostral, dorsomedial and ventrolateral quadrants of the caudate-putamen, and in the rostrobasal cell cluster, rostral pole, medial and lateral shell of the nucleus accumbens and the olfactory tubercle. The numbers of neurons responding to amph and hal in all subterritories following co-administration of the two drugs were significantly less than the summed numbers responding individually to amph and hal. Furthermore, in the subterritories where immunohistochemically detectable responses elicited by amph exceeded those produced by hal, co-administration of the two drugs resulted in responses comparable to those elicited by hal given alone. It is suggested that some of the reported anti-dopaminergic behavioral effects of basal ganglia neurotensin may be attenuated in conditions of reduced dopamine neurotransmission.

The evolving theory of basal forebrain functional—anatomical ‘macrosystems’

“…The accumbens shell, for example, appears to comprise multiple subdivisions (e.g. Ricci et al, 2004;Todtenkopf and Stellar, 2000, Todtenkopf et al, 2002, 2004Zahm et al, 1998), which, in concert with interconnected districts in cortex, diencephalon and brainstem, may operate as functional units, quite along lines proposed herein. Furthermore, it should be emphasized that distinct anatomical boundaries separating such putative functional units may not be apparent.…”

An update on the connections of the ventral mesencephalic dopaminergic complex

“…Presumably, any of these connections could exert profound modulation on through-conduction of signals in the basal ganglia. Moreover, any theory concerned with this circuitry must take into account the effects of neruopeptides such as dynorphin, substance P, enkephalins and neurotensin, which co-exist with GABA in various subpopulations of MdSNs and tier 1 neurons (e.g., Deutch et al, 1985; Kalivas, 1985; Kelley and Cador, 1988; Steiner and Gerfen, 1998; Zahm et al, 1998; Geisler and Zahm, 2006; Reynolds et al 2006). …”

Effects of neurotensin gene knockout in mice on the behavioral effects of cocaine

“…Cocaine and amphetamine administration is associated with increased NT expression in both the NAc and caudate putamen in rats (Gygi et al 1994;Hanson et al 1989;Zahm et al 1998) and mice (Betancur et al 1997). It has been speculated that these increases may be involved in behavioral responses that require chronic cocaine administration, such as sensitization, although the present data would suggest that increased NT synthesis might be more likely to be an adaptive process that limits cocaine actions.…”