Haloperidol, a
dopamine (DA) D2 receptor-preferring antagonist, produces
catalepsy whereby animals maintain awkward posture for a period of time. Sub-threshold doses of
haloperidol fail to produce
catalepsy initially, however, when the
drug is given repeatedly in the same test environment, gradual day-to-day increases in
catalepsy are observed. More importantly, if sensitized rats are injected with saline instead of
haloperidol they continue to be cataleptic in the test environment suggesting that environment-
drug associations may play a role. DA D3 receptors have been implicated in a number of conditioned behaviors. We were interested if DA D3 receptors contribute to
catalepsy sensitization and conditioning in rats. We tested this hypothesis using the DA D3 receptor-selective antagonist
NGB 2904 (0.5, 1.8 mg/kg) and the DA D3 receptor-preferring antagonist
nafadotride (0.1, 0.5 mg/kg). For 10 consecutive conditioning days rats were treated with one of the D3 receptor antagonists alone or in combination with
haloperidol (0.25 mg/kg) and tested for
catalepsy, quantified by the time a rat remained with its forepaws on a horizontal bar. On test day (day 11), rats were injected with saline or the D3 receptor antagonist and tested for conditioned
catalepsy in the previously
drug-paired environment. Rats treated with
NGB 2904 or
nafadotride alone did not develop
catalepsy. Rats treated with
haloperidol or
haloperidol plus
NGB 2904 or
nafadotride developed
catalepsy sensitization with repeated conditioning. When injected with saline they continued to exhibit
catalepsy in the test environment--now conditioned. On the other hand,
NGB 2904 (1.8 mg/kg) or
nafadotride (0.5 mg/kg) given on the test day (after sensitization to
haloperidol) significantly attenuated the expression of conditioned
catalepsy. Our data suggest that the D3 receptor antagonist
NGB 2904 (1.8 mg/kg) and
nafadotride (0.5 mg/kg) significantly attenuate conditioned
catalepsy in rats when given in test but not when given during sensitization. Results implicate DA D3 receptors in regulating the expression of conditioned
catalepsy.