Neonatal Treatment with Monoamine Uptake Inhibitors Alters Later Response in Behavioural ‘Despair’ Test to β and GABA‐B Receptor Agonists

Abstract: The administration of monoamine uptake‐inhibiting antidepressant drugs to rats during the early postnatal period was previously shown to lengthen the duration of subsequent immobility in Porsolt's swim test, hence suggesting increased behavioural ‘despair’ in these animals. Because the mechanism of the antidepressant action may be related to changes in the cerebral monoamine or γ‐aminobutyric acid (GABA) function, the present study was carried out to examine the response in the swim test to a β‐receptor agonist salbutamol, or to the GABA‐B receptor agonists progabide and baclofen in rats treated with antidepressant drugs during the second and third postnatal week: either desipramine 5 mg/kg, nomifensine 10 mg/kg or zimeldine 25 mg/kg. When tested a month later i.e. at the age of two months these rats were immobile in water for a longer period than the controls. Salbutamol 10 mg/kg and progabide 100 mg/kg increased the immobility time in the control rats but neither drug affected the rats treated with desipramine, nomifensine or zimeldine. When the animals were 5 months of age, salbutamol 10 mg/kg and baclofen 10 mg/kg shortened the immobility time in the desipramine‐treated rats. The control rats and those treated with zimeldine were not affected by the drugs. The results indicate that in the rats which were neonatally treated with antidepressants, the immobility time in water is lengthened in adulthood. Moreover, the response to β‐receptor and GABA‐B receptor agonists is increased from the response observed in the control rats. 1988 Nordic Pharmacological Society