The effect of DSP-4 on some positively reinforced operant behaviors in the rat.

The effects of a new neurotoxin for noradrenergic (NA) neurons, DSP-4, on the acquisition, retention and extinction of positively reinforced operant responses were studied in rats. The acquisition of an L-shaped runway task for food reward, of a simultaneous light-dark discrimination in a Y-maze task and of a lever press response for food was not affected in DSP-4 treated animals. No deficit in retention behavior was found in the Y-maze task after DSP-4 treatment. The DSP-4 treated animals showed increased resistance to extinction in the L-shaped runway. However, the extinction of the lever press response for food (CRF) was unaffected in the same animals. In accordance with previous results, DSP-4 resulted in a widespread depletion of NA in cortex, hippocampus, cerebellum and spinal cord. One week after the DSP-4 administration, histochemical studies at the light microscopic level indicated that the cell bodies of the locus coeruleus remained intact in DSP-4 treated animals. Desipramine pretreatment provided only partial protection from the neurotoxic effects of DSP-4. The results are discussed in relation to the mechanism by which DSP-4 produced the long-term depletion of central NA ans with reference to the role of central NA neurons in behavior.