Attenuation of water intake and operant responding by dopamine D2 antagonists: raclopride provides important cues for understanding the functional mechanism of action.
The selective dopamine (DA) D2 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 D2 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 occurred 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 D2, but not with D1, antagonists, which further supports that this apomorphine-effect is mediated via D2 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.
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
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Ljungberg
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D005116:Extrapyramidal Tracts / Q000187:drug effects; D008297:Male; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D012457:Salicylamides / Q000494:pharmacology
D018492:Dopamine Antagonists; D012457:Salicylamides; D020891:Raclopride; D001058:Apomorphine