In vivo voltammetric and behavioural evidence for somatodendritic autoreceptor control of mesolimbic dopamine neurones.

Somatodendritic autoreceptor control of mesolimbic dopamine neurones was assessed using in vivo differential pulse voltammetry to monitor dopamine metabolism in the nucleus accumbens following infusion of haloperidol or dopamine into the ipsilateral ventral tegmental area (VTA) of chloral hydrate anaesthetized rats. Haloperidol (2.5 micrograms/0.5 microliters) produced an increase in dihydroxyphenylacetic acid (DOPAC) levels (45%) whilst dopamine produced a transient decrease (38%). In three experiments this decrease was smaller and was followed by a large increase in DOPAC levels (108-208%). However, the results of radiolabelled drug diffusion studies suggested that the secondary rise in DOPAC in the nucleus accumbens may be due to diffusion of dopamine following infusion into the VTA. In a separate set of experiments rats were injected with haloperidol (2.5 micrograms/0.5 microliters) bilaterally into the VTA and their behaviour monitored using doppler shift radar. Haloperidol infusion produced a phase of increased exploratory behaviour lasting approximately 30 min. Both sets of data support previous electrophysiological studies suggesting the presence of functional dopamine somatodendritic autoreceptors in the mesolimbic system. The results further demonstrate the applicability of in vivo voltammetry for study of the effects of drugs on discrete receptor populations.