Effects of chronic food restriction on prodynorphin-derived peptides in rat brain regions

Chronic food restriction produces a variety of physiological and behavioral adaptations including a potentiation of the reinforcing effect of food, drugs and lateral hypothalamic electrical stimulation. Previous work in this laboratory has revealed that the lowering of self-stimulation threshold by food restriction is reduced by μ- and κ-selective opioid antagonists. In the present study, the effect of chronic food restriction on levels of three prodynorphin-derived peptides, namely dynorphin A_1-17 (A_1-17), dynorphin A_1-8 (A_1-8) and dynorphin B_1-13 (B_1-13) were measured in eleven brain regions known to be involved in appetite, taste and reward. Food restriction increased levels of A_1-17 in dorsal medial (+ 19.6%), ventral medial (+ 24.2%) and medial preoptic (+ 82.9%) hypothalamic areas. Levels of A_1-17 decreased in the central nucleus of the amygdala (- 35.1%). Food restriction increased levels of A_1-8 in nucleus accumbens (+ 34.4%), bed nucleus of the stria terminalis (+ 24.5%) and lateral hypothalamus (+ 41.9%). Food restriction had no effect on levels of B_1-13. A_1-17 is highly κ-preferring and the brain regions in which levels increased all have a high ratio of κ:μ and δ receptors. A_1-8 is less discriminating among opioid receptor types and the brain regions in which levels increased have a low ratio of κ:μ and δ receptors. The present results suggest that food restriction alters posttranslational processing within the dynorphin A domain of the prodynorphin precursor, possibly leading to a change in the balance between κ and non-κ opioid receptor stimulation in specific brain regions.