Effects of Dopaminergic Agonists and Antagonists on the Muscarinic and Dopaminergic Receptors from Rat Neostriatum

Abstract

This work presents the effects of dopaminergic agonists (mazindol 10 mg/kg, p.o., MAZ, and apomorphine 1 mg/kg, i.p., APO) and antagonists (pimozide 20 mg/kg, p.o., PIM, and sulpiride 100 mg/kg, p.o., SUL) on muscarinic (MR) and dopaminergic receptors (DR) in the rat neostriatum from animals treated daily during 7 days. The results (fmol/mg protein) showed that MAZ caused a 37% increase in MR. No effect was observed with PIM but it blocked the effect of MAZ. A 20% increase was seen with SUL. Its association with APO did not alter MR, but blocked MAZ effect. It was also observed that MAZ and APO tended to increase M1-like receptors (283.3 ± 15.18 and 291.9 ± 28.22, respectively), while a decrease was also seen with the association of SUL plus APO (206.2 ± 13.85). On M2-like receptors, an increase was observed with PIM plus MAZ (31.1 ± 1.78) and with APO alone (38.1 ± 1.44). The increase seen with APO was blocked by PIM and SUL (26.2 ± 1.78 and 21.2 ± 0.78, respectively). MAZ increased D2-like receptor (261.6 ± 13.63), and this effect had a tendency to be blocked by PIM and SUL (224.1 ± 18.02 and 226.6 ± 10.88, respectively). Similarly, it increased D1-like receptors (261.0 ± 16.89). A greater effect was seen with PIM plus MAZ (357.6 ± 33.72) or plus APO (307.0 ± 15.40), as related to either one alone (261.0 ± 16.89 and 156.1 ± 17.96, respectively). SUL (142.9 ± 9.95) was devoid of effect, but blocked the effect of MAZ (184.1 ± 6.96). The work showed that dopaminergic agonists and antagonists have the ability to interact with MR and to influence both systems.