Partial Deletion of Glial Cell Line-derived Neurotrophic Factor (GDNF) in Mice: Effects on Sucrose Reward and Striatal GDNF Concentrations

Glial cell line derived neurotrophic factor (GDNF) has been reported to alter the reward value of abused substances such as alcohol and cocaine as well as neural circuitry underlying reward. The role of GDNF in reward was further characterized in the present study using operant procedures to determine the value of a natural reward, sucrose, in GDNF heterozygous (GDNF+/-) mice versus wild-type (WT) mice. Female mice were tested for 2 h daily for 10 days in operant chambers with 2 levers. Responses on the correct lever allowed 5-s access to a dipper cup containing 15% sucrose. GDNF+/- and WT mice did not differ with acquisition or accuracy of responding. GDNF+/- mice emitted more responses than WT mice for sucrose, suggesting enhanced reward value of sucrose in these mice. In a separate experiment, concentrations of GDNF protein in striatal tissue were determined at 4, 8, and 12 months of age and found to be 38%-68% lower in GDNF+/- than WT mice at all three ages. Together, the results are consistent with an emerging literature indicating that reduced GDNF levels augment reward and increased GDNF levels attenuate reward, suggesting that GDNF plays an important role in neural systems mediating reward.