Table 2.

Examples of Effects of Molecular Mediators in the NAc on Depression- Versus Addiction-Like Behavior

Protein class	Protein	Effect in depression models	Effect in addiction models
Transcription factor	CREB	↑ Susceptibility	↓ Drug reward
	NFκB	↑ Susceptibility	↑ Drug reward
	ΔFosB	↓ Susceptibility	↑ Drug reward
	SRF	↓ Susceptibility	0 Drug reward
	β-catenin2	↓ Susceptibility	N/A
Signaling	BDNF-TrkB	↑ Susceptibility	↑ or ↓ Cocaine reward1, ↓ Morphine reward
	GluA2	↓ Susceptibility	↑ Drug reward
	RGS4	↓ Susceptibility3	↓ Drug reward
	Rac1	↓ Susceptibility	↓ Drug reward
	Dynorphin	↑ Susceptibility	↓ Drug reward
Epigenetic	HDAC (Class I) inhibition	↓ Susceptibility	↑ Drug reward4
	HDAC55	↓ Susceptibility	↓ Drug reward
	G9a inhibition	↑ Susceptibility	↑ Drug reward
	DNMT inhibition	↓ Susceptibility	↑ Drug reward

¹The influence of BDNF-TrkB signaling in NAc on cocaine reward is opposite in D1-type versus D2-type medium spiny neurons, although the net effect is to promote reward¹⁸.

²The influence of β-catenin is derived from studies of upstream proteins (e.g., disheveled and glycogen synthase kinase 3β)¹³¹.

³From¹⁶⁴.

⁴While short-term inhibition drives increased reward, longer-term inhibition does the opposite¹⁶⁵.

⁵A class II HDAC.