Differential interactions of picrotoxin with the biting behaviour caused by 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin and apomorphine in the guinea pig: A study of the mechanisms involved

Abstract

2-(N,N-dipropyl)amino-5,6-dihydroxytetralin (0.025–0.05 mg/kg s.c.) and apomorphine (0.25–1.0 mg/kg s.c.) each caused a dose-dependent biting behaviour in the guinea pig, 100% of animals responding with a continuous biting at the larger doses. Bilateral intrastriatal picrotoxin (0.625–5 μg/μl) did not cause biting. However, when 0.625 μg intrastriatal picrotoxin was combined with subthreshold doses of the 2-aminotetralin (0.003–0.0125 mg/kg s.c.) a dose-dependent biting response was recorded, and a continuous biting in 100% of animals could be obtained. Similarly, when a subthreshold dose of aminotetralin (0.006 mg/kg s.c.) was combined with increasing doses of intrastriatal picrotoxin (1.25–5.0 μg) a dose-dependent biting occurred and reached a maximum intensity. In contrast, similar combinations of picrotoxin and apomorphine failed to elicit biting. The continuous biting behaviour induced in 100% of animals by a combination of subthreshold doses of picrotoxin (0.625 μg intrastriatal) and the 2-aminotetralin compound (0.0125 mg/kg s.c.) was not antagonised by the bilateral intrastriatal injections of 2% procaine, noradrenaline (6.25–25μg) or dopamine (25–100 μg) but was antagonised by serotonin (100–200 μg), GABA (800–1600 μg) and the cholinergic agonist, RS86 (100–200 μg). In agreement with these observations, it was shown that the peripheral administration of an anticholinergic agent (dexetimide, 0.625–2.5 mg/kg i.p.) and an antiserotonergic agent (cyproheptadine, 1.25–5.0 mg/kg i.p.) enhanced the biting induced by a combination of 1.25 μg intrastriatal picrotoxin and 0.006 mg/kg s.c. aminotetralin (threshold for combination, producing biting in 30% control animals). In contrast, biting was not enhanced by the α- and β-adrenergic blocking agents, aceperone and di-propranolol. These data further the observations of differences in the biting responses caused by apomorphine and 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin. A complex of interactions between GABA, serotonin and acetylcholine would appear of primary importance for the mediation of abnormal peri-oral effects induced by the 2-aminotetralin compound.