DISTINCT AND INTERACTIVE EFFECTS OF D-AMPHETAMINE AND HALOPERIDOL ON LEVELS OF NEUROTENSIN AND ITS MESSENGER-RNA IN SUBTERRITORIES IN THE DORSAL AND VENTRAL STRIATUM OF THE RAT

Striatal tissue concentrations of neurotensin, expression of neurotens in/neuromedin N (NT/N) mRNA, and numbers of neurotensin-immunoreactive neurons are increased by d-amphetamine (amph), which stimulates dopam ine release in the striatum, and haloperidol (hal), a dopamine recepto r antagonist with high affinity for D2-like receptors. The possibility that the effects of these drugs involve distinct subpopulations of st riatal neurons was addressed in this study, in which the relative numb ers and distributions of striatal neuron profiles containing neurotens in immunoreactivity and/or NT/N mRNA were compared following administr ations of hal, amph, hal and amph co-administered, and vehicle. Fourte en striatal subterritories in caudate-putamen, nucleus accumbens, and olfactory tubercle were evaluated. Amph produced increases in the expr ession of neurotensin preferentially in the ventromedial and caudodors al subterritories of the caudate-putamen, the rostrobasal cell cluster and lateral shell of the nucleus accumbens, and the olfactory tubercl e. Haloperidol produced increased neurotensin expression in much of do rsal and ventral striatum, most prominently in the rostral, dorsomedia l and ventrolateral quadrants of the caudate-putamen, and in the rostr obasal cell cluster, rostral pole, medial and lateral shell of the nuc leus accumbens and the olfactory tubercle. The numbers of neurons resp onding to amph and hal in all subterritories following co-administrati on of the two drugs were significantly less than the summed numbers re sponding individually to amph and hal. Furthermore, in the subterritor ies where immunohistochemically detectable responses elicited by amph exceeded those produced by hal, co-administration of the two drugs res ulted 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 o f reduced dopamine neurotransmission. (C) 1998 Wiley-Liss, Inc.