Effect of inhibin, follistatin, or activin infusion into the lateral hypothalamus on operant behavior of rats fed lysine deficient diet

To identify brain mechanisms which mediate hunger for amino acid (e.g. l-lysine; Lys) deficiency, rats were trained to bar press (FR30 schedule) to receive 50 mg pellets of a complete diet. Rats given a lysine deficient (Lys-def) diet ad libitum maintained a high rate of bar pressing but when allowed ad libitum access to 0.4 M Lys to drink had a significant decrease in pressing. Also, Lys continuously infused by minipump into the lateral hypothalamic area (LHA) inhibits pressing by rats given a Lys-def diet. The threshold maximal dose is between 0.1–0.5 nmol Lys/h. Therefore, animals lacking dietary Lys will work to receive complete diet, but replacement of Lys by voluntary consumption or by direct infusion into the LHA inhibits bar pressing for complete diet. The ratio of brain activin and inhibin may modulate motivation to work for a complete diet, since continuous inhibin or follistatin, but not activin, infusion into the LHA was found to inhibit bar pressing, which is normally quite strong in rats maintained on Lys-def diet. The inhibitory effect of LHA inhibin infusion was replicated, and concurrent availability of Lys solution ad libitum was additive with LHA inhibin infusion to depress responding further. This inhibitory effect of inhibin or follistatin did not result from altered ad lib. consumption of Lys-def diet. Although LHA Lys infusion did decrease consumption of a concurrently available Lys solution, inhibin did not change ad libitum Lys consumption. This indicates that inhibin may work in the LHA to inhibit bar pressing for complete diet via other mechanisms than sensation of Lys deficiency.