Abstract
Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased pre-pulse inhibition, and behavioral inflexibility. In the current study, we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation, and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex (PFC), dorsal striatum (dSTR), and nucleus accumbens (NAcc). Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A deficient rats exhibited lower break points and tended to have lower “highest completed ratios.” Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the PFC we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dSTR and the NAcc. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.
Highlights
Nogo-A is an important neurite growth-regulatory protein in the developing and adult nervous system (Schwab, 2010)
We extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation, and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex (PFC), dorsal striatum, and nucleus accumbens (NAcc)
This latter point is of interest, as the behavioral and structural phenotypes of Nogo-A−/− mice and Nogo-A deficient rats make them potential tools to investigate the pathology of schizophrenia (SCZ; Kristofikova et al, 2013; Willi and Schwab, 2013)
Summary
Nogo-A is an important neurite growth-regulatory protein in the developing and adult nervous system (Schwab, 2010). The rat Nogo-A knockdown model uses the well-characterized Sprague Dawley outbred strain and offers increased translational value compared to inbred mice, which is important when evaluating a possible role of neuronal growth regulation in psychiatric disorders (Tews et al, 2013). This latter point is of interest, as the behavioral and structural phenotypes of Nogo-A−/− mice and Nogo-A deficient rats make them potential tools to investigate the pathology of schizophrenia (SCZ; Kristofikova et al, 2013; Willi and Schwab, 2013)
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