Pre- and postsynaptic responses to 1-(1-naphthylpiperazine) following adaptation to stress in rats

In view of a role of pre- and postsynaptic serotonin (5-hydroxytryptamine; 5-HT) receptors in adaptation to stress, effects of 1-(n-aphthylpiperazine) (I-NP) were compared in unrestrained and repeatedly restrained adapted rats. In the first part of the study, effects of various doses (1.0 - 15 mg/kg ip) of I-NP were monitored on brain 5-HT metabolism (presynaptic response) and on the activity (postsynaptic response) of rats in an activity cage to which the rats were habituated before the drug administration. The drug injected at doses of 2.5 - 15.0 mg/kg increased motor activity and decreased brain 5-hydroxyindoleacetic acid (5-HIAA) concentration in a dose-dependent manner. In the second part of the study, rats were restrained on wire grids 2 h/day for 5 days. First-day episode of 2-h restraint decreased 24-h cumulative food intake, water intake and growth rate. The decreases attenuated following second-, third- and fourth-day episodes of 2-h restraint were not observed following fifth-day episode of 2-h restraint stress, suggesting adaptation to the stress schedule has occurred. Serotonergic and motor responses to 1-NP in unrestrained and repeatedly restrained adapted rats were compared by injecting the drug at a dose of 5 mg/kg, a dose that above results suggested would not produce maximal effects on 5-HT metabolism or motor activity. Administration of I-NP at a dose of 5 mg/kg increased motor activity and decreased brain 5-HIAA concentration in unrestrained and repeatedly restrained adapted rats. Increases of motor activity were much greater in repeatedly restrained adapted than unrestrained rats. Decreases of 5-HIAA concentration were comparable in the two groups. The results are discussed in the context of an increase in the effectiveness of postsynaptic 5-HT-1A and 5-HT-1B receptors and a decrease in the effectiveness of presynaptic 5-HT-1A (somatodendritic) and 5-HT-1B (terminal) receptors following adaptation to stress. It is suggested that these changes of receptor responsiveness might help coping with stress demand to produce adaptation to stress. (C) 2001 Elsevier Science Inc. All rights reserved.