8-OH-DPAT, a 5-HT(1a) agonist and ritanserin, a 5-HT(2A/C) antagonist, reverse haloperidol-induced catalepsy in rats independently of striatal dopamine release

Guillaume Lucas, Norbert Bonhomme, Philippe De Deurwaerdère, Michel Le Moal, U. Spampinato
Psychopharmacology. 1997-05-15; 131(1): 57-63
DOI: 10.1007/s002130050265

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In this study, both catalepsy and changes in extracellular levels of striatal
dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) induced by the typical
neuroleptic haloperidol (HAL) were simultaneously assessed, using intracerebral
microdialysis in freely moving rats, in the presence of either the 5-HT1A agonist
8-OH-DPAT or the 5-HT2A/C antagonist ritanserin. HAL (1 mg/kg, SC) elicited a
strong cataleptic state, reaching its maximal intensity (about 240 s) 2 h after
the drug administration. This effect was paralleled by a long-lasting enhancement
of striatal DA and DOPAC extracellular levels, reaching 230 and 350% of basal
values, respectively. 8-OH-DPAT (0.1 mg/kg, SC) given 2.5 h after, and ritanserin
(0.63 and 1.25 mg/kg, IP), given 15 min prior to HAL, significantly reduced the
neuroleptic-induced catalepsy. However, both 5-HT agents failed to modify basal
DA and DOPAC striatal outflow as well as the stimulatory effect of HAL on these
parameters. It can thus be concluded that the anticataleptic effect of these
compounds is not related to an alteration of DA release within the striatum.


Auteurs Bordeaux Neurocampus