Biphasic effects of chronic saccharin intake on pain responses of healthy and diabetic rats of two genetically selected strains.

Rats of the LC-2-HI strain, selected for high rates of self-stimulation, were supplied with a 3 mM saccharin solution. Within 1 week they developed markedly prolonged latencies to painful stimuli on a hot-plate. In contrast, a similar effect became manifest in LC-2-LO rats only after 3 weeks. Both strains of rats were made diabetic by injection of streptozotocin. LO rats showed more polydipsia and hyperglycemia than HI rats and, when drinking saccharin solution, developed cross-tolerance to morphine within about 2 weeks. It is assumed that saccharin consumption stimulates the release of endogenous opioid peptides, probably via stimulation of gustatory sweet receptors. The opioid peptides exert a biphasic effect: initially they raise the pain threshold, but at a later stage they cause chronic cross-tolerance to morphine.