Dj. Sanger et G. Perrault, EFFECTS OF TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS ON RESPONSE DECREMENT PATTERNS IN RATS, The Journal of pharmacology and experimental therapeutics, 272(2), 1995, pp. 708-713
Within-session decrements in instrumental responding are a characteris
tic effect of certain neuroleptic drugs including haloperidol and pimo
zide. There is little consensus, however, as to whether these effects
can best be explained as motivational or motor deficits. A number of r
ecently developed drugs have been described as atypical antipsychotics
and are claimed to produce fewer motor side effects than more traditi
onal neuroleptics. Little work has been done to investigate whether su
ch atypical agents also give rise to within-session response decrement
s. The present experiment used the operant responding of rats to study
the effects of a range of antipsychotic drugs. Rats were trained to l
ever press for food during daily sessions (FR10 schedule) and respondi
ng was recorded during each 3-min period of the 15-min sessions. Dose-
related decreases in overall response rates were produced by all the d
rugs studied; ED50 values were: haloperidol 0.17 mg/kg, risperidone 0.
18 mg/kg, setoperone 0.23 mg/kg, remoxipride 1.2 mg/kg, sertindole 4.8
mg/kg, thioridazine 7.6 mg/kg, clozapine 8.9 mg/kg, amisulpride 34 mg
/kg, sulpiride 74 mg/kg. The presence of within-session response decre
ments was confirmed for haloperidol and demonstrated with remoxipride,
but similar effects were not observed with clozapine, thioridazine, r
isperidone, sertindole, setoperone, sulpiride and amisulpride. As a nu
mber of these drugs are known to have high affinity for 5HT(2) recepto
rs, the effects of the 5HT(2) antagonist ritanserin (1 and 10 mg/kg) w
ere studied alone and in combination with haloperidol. Ritanserin had
no effect on response rates, and did not antagonize but rather potenti
ated the effect of haloperidol. Our results show that within-session r
esponse decrements in instrumental responding are not produced by a nu
mber of atypical antipsychotic drugs and that this property appears no
t to be associated with antagonist activity at 5HT(2) receptors.