The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions

Abstract

The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50 = 32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50 greater than 100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat.

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

“…25 The system is fully computerized and uses beams of red and infrared lights in combination with vertical and horizontal photocell arrays (4 cm distance between cells) to detect movements of animals. Two different parameters were measured every 10 min for the entire recording period.…”

Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice

“…Motor activity was recorded by means of a multicage red and infrared-sensitive motion detection system. 26 Motility was defined as all movements of a distance of 4 cm or more detected by 48 horizontal photocells, and represents measurement of general activity. Locomotion was measured by counting the number of times an animal had covered eight horizontal photocells or moved from one side of the test cage to the other side (a distance of at least 32 cm).…”

Selective Effects of Low-Dose D2 Dopamine Receptor Antagonism in a Reaction-Time Task in Rats

“…However, the recently devel oped OA antagonist, raclopride, has a high affinity for the 02 OA receptor and crosses the blood-brain barrier fairly easily, reaching its peak concentration at about 15 minutes after intravenous injection (Kohler et al 1985). Raclopride has no effect on the activity of ade nylate cyclase, indicating the absence of action on the 01 receptors (Ogren et al 1986). On the other hand, the drug SCH-23390 has a very high affinity for the OA 01 receptor, as compared to its affinity for the 02 receptor (Billard et al 1984;Hyttel 1983;Hjorth and Carlsson 1988) Behavioral studies have indicated a role for the mesocorticolimbic dopaminergic system in the medi ation of the pharmacological actions of psychomotor stimulants such as amphetamine or cocaine.…”