Behavioural effects and supersensitivity following nigral dopamine receptor stimulation

Abstract

Nigrostriatal dopamine (DA)-containing neurones have the potential to modulate neostriatal output at two levels. First, DA released from the terminals of the DA-containing pars compacta neurones can act on striatal DA receptors. In addition, these pars compacta cells can release DA from their dendrites within the nigra^1–3. Dendritically released DA could act at receptors located on these same cells (‘autoreceptors’)^4,5 or at receptors which are located on other nigral elements, especially strionigral afferent fibres^4,6,7. However, although the stimulation of striatal DA receptors produces clear behavioural effects, no behavioural consequence of nigral DA receptor stimulation has been shown^8,9. We report here that nigral DA receptor stimulation can produce clear behavioural effects in the appropriate circumstances. Unilateral intranigral injections of the DA receptor stimulant, apomorphine, produce clear contralateral turning in animals that (1) had been previously given intracerebral 6-hydroxydopamine (6-OHDA) injections, which extensively damage the ipsilateral nigral DA-containing cells, or (2) had been pretreated for 1 week with the DA receptor blocker, haloperidol. In addition, the turning produced by intranigral apomorphine in 6-OHDA-treated animals was much greater when the drug was given 14–17 days after the intracerebral neurotoxin than when it was given 4–7 days after, suggesting the development of supersensitivity to apomorphine in the nigra. These results suggest that the nigra must be considered as a site of action for drugs whose main effect is on the dopaminergic system.