Increased irritability: A permanent behavior change induced in the rat by intraventricular administration of 6-hydroxydopamine

Intraventricular injection of 2 doses of 300 μg of 6-hydroxydopamine (6-OHDA) into rats induced an increased reactivity to exogenous (non-painful) stimuli. This increased irritability lasted more than 4 months (the longest period studied) and consisted of crying, hissing, urination, defecation, standing in an upright posture, biting and panic jumping. The degree of irritability was inversely correlated with the level of brain norepinephrine (NE). The uptake of 3H-NE into all brain regions studied was decreased after administration of 6-OHDA. The rate of 3H-NE decay from the brain stem (hypothalamus, medulla-pons) was delayed 1 week and accelerated 9 weeks after 6-OHDA administration. The decay of 3H-NE from the residual parts of the brain was enhanced both 1 and 9 weeks after 6-OHDA injection. Diazepam, chlordiazepoxide and meprobamate suppressed the increased irritability at doses which did not cause muscle relaxation. The normalization of the behavior produced by diazepam was accompanied by a normalization of the rate of 3H-NE decay both in the brain stem and the residual parts of the brain. The neuroleptics chlorpromazine and haloperidol were effective in abolishing the increased irritability only at strongly sedative doses.