The origin of the dopamine nerve terminals in limbic and frontal cortex. Evidence for meso-cortico dopamine neurons (original) (raw)

Thierry et al. 16 described dopamine (DA) stores in the cortex cerebri and were the first to suggest the existence of cortical DA nerve terminals. Subsequent pharmaco-histochemical studies using recent sensitive modifications of the Falck-Hillarp technique2,6,13 together with DA-fi-hydroxylase inhibitors 15 and L-DOPA combined with peripheral decarboxylase inhibitors after reserpine pretreatment have confirmed and extended this study to show that cortical DA nerve terminals probably exist but mainly in the limbic cortex and in the deep layers of the frontal cortex 7,s,11,12. In order to obtain information as to the origin of these cortical DA nerve terminals, lesions have been made in the ventromedial tegmental area of the midbrain, rich in DA nerve cell bodies (group A9-A10 according to DahlstrSm and Fuxe 4) and in the hypothalamic catecholamine (CA) cell group A13 a,5 localized in the dorsal hypothalamus. Male Sprague-Dawley rats (body wt. 150-250 g) have been used. Most of the electrolytic lesions (0.5 mA DC, 30 sec, unipolar) were performed in the area between the A9 and A10 group (Fig. 1). The coordinates were according to K6nig and KlippeP as follows: A (anterior) = +2.0 mm; L (lateral) = + 1.0 mm; V (vertical) ~-2.8 mm. Unilateral intracerebral injections with 6-hydroxydopamine (6-OH-DA, 16 #g/8 /~1) were also performed (A-+ 2.5; L = + 1.2; V =-2.4). Two rats received electrolytic lesions in the midline (L = 0) at the same level and depth as above in order to destroy mainly the A10 group. Also a lateral lesion with the same electrical parameters as above was made in one rat in order to avoid lesioning the A10 group (A = +1.95; L = +1.8; V =-2.8). The A13 group was lesioned in two rats using the following coordinates: A = +4.9 mm; L = +0.6 m m ; V =-1.8 mm. In this case the DC current was 1 mA. All the lesions were unilateral and the non-lesioned side served as a control. The degree of anterograde degeneration of the DA systems to the forebrain was studied 2-3 weeks following the lesion. The DA nerve terminals were distinguished from the noradrenaline (NA) and 5-hydroxytryptamine (5-HT) nerve terminals by using the recent discovery that in the forebrain reserpine-resistant accumulations of CA seem to occur exclusively in the DA nerve terminals 7,11. Some rats were therefore pretreated with reserpine (5-10 mg/kg, i.p.) 18-24 h before killing.