Attenuation of Water Intake and Operant Responding by Dopamine D2 Antagonists: Raclopride Provides Important Cues for Understanding the Functional Mechanism of Action

Abstract: The selective dopamine (DA) D 2 receptor antagonist raclopride was found to attenuate operant lever‐pressing with water as reward in a dose dependent manner and more potently than the corresponding consummatory act, i.e. the unconditioned water intake. This is the same way as previously reported for other DA D 2 antagonists. In screening experiments raclopride has been selected on the basis of great separation between antagonism of DA‐agonist induced hyperactivity, stereotypies and production of catalepsy. We found that attenuation of lever‐pressing and water intake by raclopride were not more separated in dose than after, for example, haloperidol. We further found that attenuation of lever‐pressing and water intake occured in doses relatively lower than those producing catalepsy, thus excluding catalepsy as a cause for the attenuation. Decreased water intake in thirsty animals caused by a low dose of apomorphine (APO) was counteracted by raclopride. This has previously been found with DA D 2 , but not with D 1 , antagonists, which further supports that this apomorphine‐effect is mediated via D 2 receptors. However, raclopride only showed this antagonism in a narrow dose‐range, like haloperidol. The selective profile previously found for sulpiride, proposed to be related to low incidence of extrapyramidal side‐effects in the clinic, was thus not replicated.