PICOLINIC-ACID BLOCKS THE NEUROTOXIC BUT NOT THE NEUROEXCITANT PROPERTIES OF QUINOLINIC ACID IN THE RAT-BRAIN - EVIDENCE FROM TURNING BEHAVIOR AND TYROSINE-HYDROXYLASE IMMUNOHISTOCHEMISTRY

Previous results suggest that the tryptophan metabolite, picolinic aci d may have the unusual properties of antagonizing the neurotoxic but n ot the neuroexcitant effects of another tryptophan metabolite, quinoli nic acid in the central nervous system. The present experiments tested this possibility utilizing behavioural and tyrosine hydroxylase immun ohistochemical techniques. In the first series of experiments, rats re ceived injections of relatively high concentrations of 6-hydroxydopami ne (12 mu g in 1 or 2 mu 1), quinolinic acid (120 nmol in 0.5 mu 1), p icolinic acid (480 nmol in 0.5 mu 1) or co-treatments (0.5 mu 1) with quinolinic (120 nmol) plus picolinic acid (480 nmol) into the region o f the substantia nigra. Results revealed that 6-hydroxydopamine and qu inolinic acid alone produced a large loss of tyrosine hydroxylase-posi tive cells in the pars compacta of the substantia nigra. Behavioural r esults for all 6-hydroxydopamine (n = 10) and for some quinolinate-tre ated rats (n = 5) revealed ipsi- and contraversive circling following amphetamine (1 mg/kg, i.p.) and apomorphine (0.5 mg/kg, s.c.), respect ively, consistent with unilateral loss of dopamine cells in the substa ntia nigra. The remaining quinolinate-treated rats (n = 9) circled ips iversively following either stimulant suggesting damage to the pars re ticulata. Groups treated with picolinic acid alone (n = 6) or co-injec ted (n = 6) showed no loss of tyrosine hydroxylase-positive cells in t he substantia nigra and no circling response to the stimulants. In the second series of experiments, low concentrations of quinolinic acid ( 2.5, 5.0, 7.5 nmol), picolinic acid (10, 20, 30 nmol), or the two toge ther (7.5 plus 30 nmol, respectively) were microinjected (0.5 mu 1) in to the dorsal striatum and circling behaviour evaluated. These results revealed dose-dependent contralateral circling with either quinolinat e or picolinate; co-injection of the two tryptophan metabolites also p roduced contralateral circling. It was concluded that picolinic acid b locks the neurotoxic but not the neuroexcitant effects of quinolinic a cid.