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A soluble fraction was extracted from a chemically deafferentiated striatum of adult Wistar rats after unilateral lesioning of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) injection. The soluble extract from the lesioned side enhanced the survival of cultured mesencephalic dopamine (DA) neurons of 14-day-old rat embryos as evidenced by quantitative counting of tyrosine hydroxylase-like immunoreactive cells. The neurotrophic activity of this striatal extract for DA neurons was highest 14 days after 6-OHDA injection and became negligible in 28 days. The extract showed no promoting effects on cultured γ-aminobutyric acid (GABA)-containing mesencephalic neurons. These observations indicate that the striatum of adult rats may initiate de novo synthesis of trophic substance(s) for DA neurons but not for GABA neurons when subjected to nigral dopaminergic deafferentiation.

Unilateral stereotaxic microinjection of a small amount of kainic acid (KA) into the nucleus tegmenti pedunculopontinus pars compacta (TPC) of male Wistar rats produced constant ipsiversive circling behavior. The rate of the TPC-derived circling was significantly attenuated by blocking agents of dopamine systems, including haloperidol and alpha-methyl-tyrosine (both injected intraperitoneally) and also 6-hydroxydopamine (injected into the bilateral medial forebrain bundles). Administration of norepinephrine antagonists (phenoxybenzamine hydrochloride and DL-propranolol) had no effect on the rate of the TPC-derived circling. Bilateral preinjections of atropine sulfate into the ventral midbrain tegmentum, including the ventral tegmental area and the pars compacta of the substantia nigra, significantly attenuated the rate of the circling. The unilateral KA injection into the TPC dramatically increased the ratio of HVA + DOPAC/dopamine, an indicator of dopamine turnover, in the nucleus accumbens as well as in the striatum bilaterally. The increase of the ratio in the nucleus accumbens was selectively suppressed by pretreatment with atropine sulfate administered into the bilateral ventral midbrain tegmentum. These facts indicate: (1) the TPC-derived circling behavior is mediated by the dopamine system, (2) the chemical stimulation of TPC by KA might produce an activation of midbrain dopamine neurons by excitatory TPC efferents to the dopamine neurons and enhance the dopamine turnover in the nucleus accumbens as well as in the striatum, (3) the excitatory TPC efferents may be muscarinic cholinergic in accordance with previous reports.