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.