EFFECTS OF SUBSTANCE P INJECTED INTO THE SUBSTANTIA NIGRA

Abstract

1 Behavioural and biochemical effects of substance P (SP, 1 to 10 μg) administered in a small volume to discrete areas of the rat's brain were studied by means of a refined microinjection technique. 2 SP injected unilaterally into the zona reticulata of the substantia nigra elicited dose-dependent contraversive circling and an increase in dopamine turnover in the ipsilateral striatum. SP applied to the zona compacta or zona lateralis, or to the medial lemniscus, evoked ipsiversive turning with a fall in dopamine turnover and a rise in 5-hydroxytryptamine (5-HT) turnover in the corresponding striatum. 3 In both cases the onset of turning was immediate, reached a peak at about 5 min and lasted for 10 min. Both types of behaviour were blocked by haloperidol and exaggerated by nialamide. 4 Unilateral injections of SP given into the crus cerebri, zona incerta, caudate nucleus, putamen or globus pallidus did not modify the animal's behaviour. 5 In rats pretreated with apomorphine or amphetamine, SP induced contraversive circling which was followed by locomotion in the opposite direction. 6 Turning responses to a second dose of SP were diminished at 3 h and reproducible at 24 h after the first injection. 7 Bacitracin (50 ng) injected into the zona reticulata caused ipsiversive turning. Larger intranigral doses of bacitracin (10 μg), as with intracisternal SP (10 μg), evoked ‘barrel rotation’. 8 No changes in the free concentrations of aspartate, glutamate, γ-aminobutyric acid, glycine or alanine were detected in any brain region following an intracisternal injection of 10 μg SP, although glutamine levels were elevated throughout the brain 30 to 60 min later.