Gadd CA, Murtra P, Hall CN, Gana M, Webber MJ, De Felipe C, Hunt SP (2001) NK1-expressing neurons critical for morphine reward behaviors in mice: C-fos expression and ablation of NK1-expressing neurons. Neuroscience 2001 Abstracts 224.13. Society for Neuroscience, San Diego, CA.
Summary: We have previously shown using conditioned place preference (CPP) that mice lacking the preferred receptor for substance P (NK1) show an absence of the rewarding response to morphine as well as reduced conditioned place aversion and physical withdrawal signs following chronic opiate treatment (Nature 405, 180-183). To locate those regions of the brain in which NK1-expressing neurons are crucial for opiate-mediated reward behavior, we examined the expression of c-Fos following acute (10 mg/kg IP) and chronic (increasing doses from 10 to 100 mg/kg IP) morphine administration, and following CPP to morphine (7.5 mg/kg) in wild-type and NK1 knockout mice. The expression of c-Fos in the brains of mice treated with chronic or acute morphine treatment was similar in both genotypes. Moreover, NK1-expressing neurons in the striatum and nucleus accumbens (NAc) were never seen to co-express c-Fos immunoreactivity. In contrast, the expression of c-Fos following the CPP protocol was significantly different between genotypes with a reduced number of c-Fos positive neurons in NK1 knockout mice in the amygdala and hippocampus but not in the NAc or dorsomedial striatum (DMS). We next investigated the effects of selective ablation of NK1 expressing neurons by injecting substance P-saporin into these regions. Our results suggest that destruction of these cells in the amygdala but not in the NAc or DMS causes a reduction in CPP to morphine without affecting anxiety levels or locomotor activity.
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