Comparison of hyperactivity in adult rats induced by neonatal intraventricular 6-hydroxydopamine following pargyline or desmethylimipramine treatment

Abstract

The relative roles of norepinephrine (NE) and dopamine (DA) in sustaining neonatal hyperactivity were assessed in rats given 6-hydroxydopamine (6-OHDA) neonatally into the lateral ventricles after pargyline (P) or desmethylimipramine (DMI) pretreatment.

On day 5 after birth, male and female rat pups were pretreated with P (50 mg/kg IP) or DMI (25 mg/kg IP) 30 min before receiving bilateral injections of 6-OHDA (200 μg/5 μl saline containing ascorbic acid 1.0 mg/ml) into the lateral ventricles. Controls were pretreated with P or DMI and then received injections of saline containing the ascorbate.

Spontaneous activity was measured in a stabilimeter at ages 30–31, 42–45, 60–63, 75–77, and 120–122 days. Activity in controls and P+6-OHDA animals was also measured at 254 days of age. The sessions lasted 45 min, except those testing activity in the 254-day-old rats which lasted 12 h.

Regional assays of catecholamines carried out when the animals were 150 days old revealed that in the P+6-OHDA group the levels of NE were reduced in frontal cortex (7% of control levels), caudate (21%), and hippocampus (14%). The NE levels were unchanged or slightly elevated in hypothalamus, ventral midbrain, and pons. The DA levels in the P+6-OHDA group were depleted in caudate (8%) and ventral midbrain (32%), and unchanged in hypothalamus and pons.

In the DMI+6-OHDA group the NE levels were reduced in caudate (25%) and elevated in hippocampus (188%). The DA levels were depleted in caudate (3%) and ventral midbrain (22%).

Both treatments resulted in long-term hyperactivity, but the syndrome was of larger magnitude and more permanent in the P+6-OHDA group. The possible biochemical basis of these differential effects is discussed.