Involvement of dopamine autoreceptors in the hypoactivity induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice.

Abstract

The effect of 8-OH-DPAT, a 5-HT1A receptor agonist, on the locomotor activity was analyzed in Albino Swiss mice. The studied drug (0.5-5 mg/kg) inhibited the spontaneous locomotor activity in mice. The hypoactivity induced by 8-OH-DPAT (1.5 mg/kg) was abolished by the dopamine (D1 and D2) receptor antagonist-haloperidol (0.00125 and 0.0025 mg/kg, but not in higher doses) and by the D2 antagonist with affinity for 5-HT1A and 5-HT2 receptors-spiperone (0.0025 and 0.005 mg/kg, but not in higher doses). The effect of 8-OH-DPAT was slightly reduced by the alpha 2-adrenoceptor antagonists: idazoxan (4 mg/kg), yohimbine (2 and 4 mg/kg) and rauwolscine (4 mg/kg). On the other hand, the non-selective 5-HT antagonist metergoline (0.5-4 mg/kg), the 5-HT1A antagonist NAN-190 (0.5-2 mg/kg), the beta-adrenoceptor blockers with high affinity for 5-HT1A and 5-HT1B receptors: pindolol and SDZ 21009 (2-8 mg/kg) and the agonist/antagonist of 5-HT1A receptors ipsapirone (2.5 and 5 mg/kg) did not affect the 8-OH-DPAT-induced hypoactivity. The obtained results suggest that the reduction of the spontaneous locomotor activity induced by 8-OH-DPAT results from a stimulation of dopamine autoreceptors, but not 5-HT receptors. Involvement of an alpha 2-adrenergic mechanism cannot be excluded.