Unexpected potentiation by discriminant benzamide derivatives of stereotyped behaviours elicited by dopamine agonists in mice

Summary

Among four stereotyped manifestations that can be simultaneously quantified in mice treated with apomorphine (APO), two of them (climbing and sniffing) emerge at low APO dosages (below 1 mg/kg) whereas licking and sniffing require APO dosages above 6 mg/kg. However, in mice pretreated (either i.p. or i.c.v.) with sulpiride (especially the levo isomer) or (±)amisulpride in moderate dosage stereotyped licking and sniffing are elicited by APO in much lower dosage (0.75 mg/kg). As a consequence, in mice pretreated with these benzamide derivatives and receiving 0.75 mg/kg APO, a biphasic effect was observed: licking and gnawing progressively appear at low dosages, whereas they are progressively abolished at higher dosages.

This potentiation of the effects of APO by (±)amisulpride is even more obvious (maximal scores increased) with larger test-doses of the dopamine agonist (up to 5 mg/kg). Amisulpride also allows the emergence of the two stereotyped behaviours in mice receiving other dopamine agonists in subthreshold dosages (Dipropyl 5,6-ADTN, dexamphetamine or cocaine). The potentation of APO is still observed after dopamine depletion by reserpine and α-methylparatyrosine, whereas that of dexamphetamine is abolished. In contrast with the benzamide derivatives, haloperidol does not potentiate at any dosage the effect of APO but, at 0.15 mg/kg, suppresses licking and gnawing elicited by 0.75 mg/kg APO in mice pretreated with 6.25 mg/kg amisulpride or veralipride.

Among a series of dopamine antagonists belonging to various chemical classes, only a number of discriminant benzamide derivatives (DBD), previously shown to differentially antagonise several APO-induced behavioural manifestations in rats (sulpiride, amisulpride, tiapride, sultopride, DO 701, LUR 2366 but not metoclopramide) potentiate APO (0.75 mg/kg) regarding licking and gnawing. In contrast, potentiation is not observed, even for a higher test dose of APO, with haloperidol, thioproperazine, pimozide, mezilamine, thioridazine or metoclopramide at any dosage tested.

For the various DBD, the two stereotyped behaviours emerge at dosages at which climbing starts to be inhibited, suggesting that selective blockade of some inhibitory response to APO is responsible for the potentiation. Among other hypothesis the possibility that the peculiar behavioural properties of DBD is related to their differential recognition of two classes of dopaminergic binding sites is discussed.