Effects of adolescent morphine exposure on brain stimulation reward sensitivity and dopamine neuron excitability

Adolescent substance abuse drives lasting changes in reward processing and decision making. To determine the effects of opioid treatment and withdrawal on reward sensitivity during adolescence, we used a rate-frequency (RF) intracranial self-stimulation (ICSS) paradigm in adolescent rats. On PD28, rats were implanted with stimulating electrodes in the medial forebrain bundle at the level of the lateral hypothalamus and trained twice-daily to perform a variant RF ICSS task tailored for adolescents. Morphine (5 mg/kg) or saline (0.5 ml/kg) was injected daily prior to the AM ICSS session from PD45-51 and we continued to perform sessions through PD60 to measure withdrawal. Rats were then trained on a standard adult RF ICSS task. All animals were tested from PD90-96 while undergoing daily morphine administration (10mg/kg) and for an additional 9 days of withdrawal. In adolescent controls, reward sensitivity was stable across baseline, injection, and post-injection sessions. Adolescent morphine administration resulted in a significant increase in reward sensitivity relative to controls followed by a reduction lasting for the entire 9-day withdrawal period. Re-exposure to morphine in adulthood resulted in a greater increase in sensitivity during administration and a more profound suppression in withdrawal relative to those that had not been exposed to morphine in adolescence. In a separate group of animals, withdrawal from adolescent morphine treatment resulted in reduced electrophysiological excitability of ventral tegmental area dopamine neurons that may contribute to lasting alterations in reward sensitivity. Such alterations following adolescent morphine exposure may drive susceptibility to maladaptive behaviors in adulthood.