Lever pressing for food reward and in vivo voltammetry: evidence for increases in extracellular homovanillic acid, the dopamine metabolite, and uric acid in the rat caudate nucleus.

Linear sweep voltammetry at chronically implanted carbon paste electrodes was used to study extracellular levels of homovanillic acid, a metabolite of dopamine, in the caudate nucleus of freely moving rats. Local infusion of homovanillic acid close to the electrode confirmed that peak 3, at about 550 mV, could be used for this purpose. Thirty minutes of lever pressing for food reward was followed by an increase in homovanillic acid, maximal about 30 min later (+42%). An earlier and larger (+51%) increase in peak 2 (350-400 mV) was seen, highly correlated (r = 0.98) with the rate of lever pressing across individuals. A smaller decrease (-23%) in peak 1 (200 mV; ascorbic acid) was seen 75 min after the behavioural session. Administration of allopurinol, an inhibitor of uric acid production, selectively abolished peak 2. Allopurinol prior to lever pressing reduced the increase in peak 2 very substantially (by 77%), confirming that this too was mainly due to uric acid. These results indicate that linear sweep voltammetry can be used to study the time course of changes in dopamine metabolism, and in other neurochemicals, in individual freely moving rats in relation to behaviour under experimental control. More specifically, they demonstrate directly that rewarded lever pressing increases dopamine metabolism in the caudate, which had previously only been inferred from indirect approaches. The level of uric acid is also increased, and it is suggested that this may serve as an index of metabolic activity.