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Prevention by (±)‐8‐hydroxy‐2‐(di‐ n propylamino)tetralin of both catalepsy and the rises in rat striatal dopamine metabolism caused by haloperidol
Author(s) -
Andersen Heidi L.,
Kilpatrick Ian C.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15419.x
Subject(s) - haloperidol , catalepsy , nucleus accumbens , endocrinology , chemistry , medicine , dopamine , 3,4 dihydroxyphenylacetic acid , caudate nucleus , putamen , agonist , 5 ht1a receptor , neurochemical , homovanillic acid , biology , serotonin , 5 ht receptor , receptor
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‐methoxyphenylacetic acid (HVA), was measured in three microdissected brain regions of the rat following a quantitative assessment of catalepsy. 2 Haloperidol alone (2.66 μzmol 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 Haloperidol significantly increased the DOPAC (by 2 to 4 fold) and HVA (by 3 to 7 fold) contents of the caudate‐putamen, nucleus accumbens and medial prefrontal cortex. Given alone, only the lower dose of 8‐OH‐DPAT caused a significant biochemical change, a doubling of cortical DOPAC. 4 In the cases where catalepsy was prevented by either dose of 8‐OH‐DPAT, the haloperidol‐induced increases in DOPAC and HVA were consistently 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 haloperidol‐induced rises in cortical DOPAC. In the nucleus accumbens, 8‐OH‐DPAT did not affect the haloperidol‐induced increases in the dopamine metabolites, irrespective of the dose employed or the resulting behaviour. When catalepsy was not prevented, 8‐OH‐DPAT did not alter the neurochemical responses to haloperidol in any region. 5 These results suggest that part of the mechanism by which 8‐OH‐DPAT prevents haloperidol‐induced catalepsy is reflected by a reversal of the compensatory increase in meso‐striatal and/or meso‐cortical dopamine neuronal activity that normally accompanies postsynaptic dopamine receptor blockade with haloperidol.