Neuronal mechanisms involved in drug-induced jumping behavior in mice

Previously we have found that lithium chloride (250 mg/kg i.p.) plus haloperidol (4 mg/kg i.p.), or apomorphine (0.25 mg/kg i.p.) plus thyrotropin releasing hormone (TRH, 20 mg/kg i.p.), elicited a jumping behavior which involves dopaminergic and cholinergic inhibition, and noradrenergic activation. Pretreatment with antiserotonergic agents such as methysergide (5 and 10 mg/kg i.p.) and cyproheptadine (5 mg/kg i.p.) enhanced the jumping behavior induced by these drugs. 5-Methoxy-N,N-dimethyltryptamine (5-MDMT, 5 mg/kg i.p.), a serotonergic receptor agonist, inhibited the jumping behavior. Muscimol, a GABA receptor agonist, at 2 mg/kg, potentiated jumping. GABA receptor antagonists such as bicuculline (4 mg/kg i.p.) and picrotoxin (0.2 and 1 mg/kg i.p.) depressed jumping. An antihistamine agent, diphenhydramine (5 mg/kg i.p.), also potentiated the jumping behavior. Furthermore methysergide (10 mg/kg i.p.), but not muscimol (2 mg/kg i.p.) elicited jumping behavior when combined with clonidine (0.5 mg/kg i.p.), TRH (20 mg/kg i.p.), haloperidol (4 mg/kg i.p.) or atropine (5 mg/kg i.p.). These results suggest that in addition to dopaminergic, cholinergic and noradrenergic mechanisms, serotonergic inhibition may be directly contributing to the initiation of jumping behavior, whereas GABAergic activation appears to be a modulating factor in this behavior.