3.4.1.3. Dynorphin
Androgens increase concentrations of dynorphin in most brain regions. For instance, chronic treatment with nandrolone significantly increases dynorphin concentrations in the hypothalamus, striatum, and PAG in intact male rats (Johansson et al., 2000a). Similarly, castration decreases dynorphin concentrations in the anterior pituitary (Molineaux et al., 1986; Fullerton et al., 1989), and these decreases can be partially reversed by subchronic (2-day) treatment with testosterone (Molineaux et al., 1986) and fully reversed by chronic (7-day) treatment with DHT (Fullerton et al., 1989).
Interestingly, the nucleus accumbens is an exception to the androgen-induced increase in dynorphin concentrations seen in other brain regions. Chronic treatment with nandrolone significantly decreases dynorphin concentrations in the nucleus accumbens in intact rats (Johansson et al., 2000b). The nucleus accumbens receives dopaminergic afferents from the ventral tegmental area and is a critical structure involved in motivated behavior, drug reinforcement, and addiction. Dynorphin inhibits dopaminergic activity in the nucleus accumbens (Muschamp & Carlezon, 2013), and androgen-induced reductions in dynorphin should theoretically increase accumbal dopamine concentrations; however, evidence for this possibility is mixed (cf., Birgner et al., 2007; Silva et al., 2009; Triemstra et al., 2008).
Androgen-induced modulations in dynorphin may be explained, in part, by androgen-induced modulations in dynorphin-converting enzyme (DCE). DCE transforms dynorphins into enkephalins via cleavage of the dynorphin peptide (Silberring et al., 1992), and DCE concentrations are under regulatory control by androgens. For example, chronic nandrolone administration significantly decreases DCE concentrations in regions that typically exhibit an increase in dynorphin concentrations following androgen treatment, including the caudate putamen, hypothalamus and PAG (Magnusson et al., 2007). In contrast, nandrolone treatment significantly increases DCE concentrations in the nucleus accumbens (Magnusson et al., 2007), which exhibits a significant decrease in dynorphin concentrations following androgen treatment.