PREVENTION BY (+ -)-8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRA OF BOTH CATALEPSY AND THE RISES IN RAT STRIATAL DOPAMINE METABOLISM CAUSED BY HALOPERIDOL/

1 The influence of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH- DPAT) on haloperidol-induced increases in the dopamine metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacet ic acid (HVA), was measured in three microdissected brain regions of t he rat following a quantitative assessment of catalepsy. 2 Haloperidol alone (2.66 mu mol kg(-1), i.p.) caused a robust cataleptic response. Given 30 min after haloperidol, 8-OH-DPAT (76 or 760 nmol kg(-1), s.c .) prevented catalepsy in 30% and 100% of rats, respectively. 3 Halope ridol significantly increased the DOPAC (by 2 to 4 fold) and HVA (by 3 to 7 fold) contents of the caudate-putamen, nucleus accumbens and med ial prefrontal cortex. Given alone, only the lower dose of 8-OH-DPAT c aused a significant biochemical change, a doubling of cortical DOPAC. 4 In the cases where catalepsy was prevented by either dose of 8-OH-DP AT, the haloperidol-induced increases in DOPAC and HVA were consistent ly lower in the caudate-putamen. This pattern was true for the rise in cortical HVA but only in response to the lower dose of 8-OH-DPAT. In contrast, neither dose of 8-OH-DPAT was able to influence the haloperi dol-induced rises in cortical DOPAC. In the nucleus accumbens, 8-OH-DP AT did not affect the haloperidol-induced increases in the dopamine me tabolites, irrespective of the dose employed or the resulting behaviou r. When catalepsy was not prevented, 8-OH-DPAT did not alter the neuro chemical responses to haloperidol in any region. 5 These results sugge st that part of the mechanism by which 8-OH-DPAT prevents haloperidol- induced catalepsy is reflected by a reversal of the compensatory incre ase in meso-striatal and/or meso-cortical dopamine neuronal activity t hat normally accompanies postsynaptic dopamine receptor blockade with haloperidol.