MODIFICATIONS IN GLUTAMATERGIC TRANSMISSION AFTER DOPAMINE DEPLETION OF THE NUCLEUS-ACCUMBENS - A COMBINED IN VIVO IN VITRO ELECTROPHYSIOLOGICAL STUDY IN THE RAT/

The interaction between the glutamatergic and dopaminergic input in th e nucleus accumbens was examined by studying the effects of dopamine d epletion of the nucleus accumbens on the local field potentials, and t he L-glutamate elicited responses of the nucleus accumbens in anaesthe tized rats in vivo. A characteristic field potential in the nucleus ac cumbens is evoked by electrical stimulation of the fornix/fimbria fibr es, with a monosynaptic positive peak at 10 ms (P10). Rats were unilat erally injected with 6-hydroxydopamine in the nucleus accumbens. The c ontralateral accumbens was sham lesioned. The rats were divided into s hort-term and long-term survival groups of one to two weeks and 24 wee ks, respectively. In the short-term group, a striking increase (up to three times) of the amplitude of the P10 components at the site of the lesion, compared with the sham lesioned contralateral accumbens and u ntreated rats, was found. The long-term group could still display a sl ight increase although on average this was not significantly different from controls. In the short-term group, at the centre of the lesion, the paired-pulse facilitation ratio was significantly smaller than at the more ventral, less denervated, border of the accumbens. These diff erences were no Longer visible in the long-term group. Single-unit act ivity of the accumbens, elicited by the iontophoretical application of L-glutamate showed, in controls, a maximal firing frequency ranging f rom 5 to 40 Hz (mean 25 Hz), whereas in the short-term group more than 50% of the accumbens neurons fired with higher frequencies, reaching up to 90 Hz (mean 55 Hz). In the long-term group the firing frequency varied from 5 to 60 Hz (mean 41 Hz). No changes in threshold ejection glutamate current were found for both lesioned groups. In control rats the L-glutamate elicited responses of six cells tested could be suppr essed by dopamine whereas in lesioned rats three of the six cells test ed were unresponsive to dopamine. Intracellular recordings of accumben s cells in slices in 6-hydroxydopamine and sham lesioned rats, showed no significant changes in the intrinsic membrane properties, e.g. rest ing membrane potential, input resistance, spike threshold, action pote ntial amplitude or duration. We conclude that dopamine denervation lea ds to an increase of excitability of the principal accumbens neurons. This is reflected by the increase of the firing frequency of these cel ls and of the amplitude of the evoked field potentials. The former is more likely of postsynaptic origin whereas the latter may also have a presynaptic contribution. These effects cannot be attributed to change s in intrinsic membrane properties of the cells.