Treatment with single doses of the antidepressant drugs, desipramine (DMI) and mianserin (MIA) was performed 2.5 and 8 hr, respectively, before the start of the experiment in order to approximate the amount of drugs still present in the brain 24 hr after the last injection of a long-term treatment. The effects of this treatment with single doses of DMI and MIA on neurotransmission in the hippocampal slice, were studied by examining the actions of serotonin (5-HT), isoprenaline and (+/-)-baclofen on the population spike of the pyramidal cell layer, recorded in area CA1. The inhibitory responses to 5-HT (1-10 microM) and (+/-)-baclofen (0.3-3 microM) were not affected by treatment with either antidepressant drug. Single doses of DMI but not of MIA, attenuated the excitatory responses to isoprenaline (0.1-1 microM). These results suggest that the present study with single doses provides information to help in the understanding of delayed adaptive changes induced by antidepressants and that the DMI-induced decrease in the beta-adrenergic response in the hippocampus is not limited to long-term treatment.