Effect of desipramine during infancy and preweanling on dorsal striatal dopamine D1 and D2 receptor binding in adolescence in the rat.
Desipramine, a monoamine uptake inhibiting antidepressant, was given once a day sc from the 6th to the 22nd postnatal days, which is during infancy and preweanling in ontogenesis, to rats and its effects on dorsal striatal dopamine D1 and D2 receptor binding in adolescence were examined. The rats were decapitated, their dorsal striata were dissected on approximately the 34th postnatal day, and the maximal densities (Bmax) and affinities (Kd) of dopamine D1 and D2 receptors were assayed using [3H] SCH 23390 and [3H] spiperone as ligands. Desipramine did not affect the densities or affinities of dopamine D1 or D2 receptor binding, and tended to increase the D1/D2 density ratio. The Bmax of dopamine D2 receptors was higher in male than in female rats (p<0.01), the D1/D2 Bmax ratio tended to be lower in male than in female rats (p<0.07), and the Kd for D1 receptors tended to be lower in male than in female rats (p<0.05). There was no interaction between treatment and gender. We conclude that desipramine given at infancy and preweanling increases the susceptibility of adolescent rats to behavioral effects of dopamine agonists with an optimal, and relatively high SCH 23390/spiperone binding site density ratio. Furthermore, gender differences in dorsal striatal spiperone binding site densities, SCH 23390/spiperone density ratio, and SCH 23390 affinities may render male rats more vulnerable than female rats to expression of excessive stereotyped behavior.
Hilakivi
I
I
Department of Physiology, Institute of Biomedicine, Faculty of Medicine, University of Helsinki, Finland.
Rinne
J
J
Marjamäki
P
P
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012727:Sex Characteristics; D012737:Sex Factors; D013134:Spiperone / Q000378:metabolism; D014316:Tritium
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D013134:Spiperone; D003891:Desipramine