CHRONIC PARENTERAL ANTIDEPRESSANT TREATMENT IN RATS - UNALTERED LEVELS AND PROCESSING OF NEUROPEPTIDE-Y (NPY) AND CORTICOTROPIN-RELEASING HORMONE (CRH)

We have previously reported elevated brain tissue contents of neuropeptide Y-like immunoreactivity (NPY-LI) following 3 weeks of oral treatment with the antidepressants zimelidine and imipramine. Other studies have not reproduced this finding. To eliminate the possibility that this has been due to insufficient treatment duration, dosage, or differences in route of administration or assay specificity, we have administered the selective serotonin reuptake inhibitor citalopram and the preferential noradrenaline reuptake inhibitor desmethylimipramine parenterally for 6 weeks. NPY-LI was assayed using both the assay employed in the original study, and an assay based on a different antiserum which has been extensively examined for cross-reactivity. To exclude the possibility that differential processing rather than altered synthesis rate is responsible for apparent changes in NPY-LI, HPLC analysis of immunoreactive fragment profiles was used. No differences in NPY-LI levels were seen in the brain regions examined, and no differences in HPLC profiles of NPY-LI were present with either drug. We conclude that chronic parenteral administration of antidepressant drugs in naive (non-depressed) animals does not affect the synthesis or processing of NPY. Another neuropeptide implicated in mechanisms of depression, corticotropin-releasing hormone (CRH) was also found to be unaffected by a similar analysis.