Chunk #28 — 2. Neural substrates for the negative emotional state associated with addiction — 2.1. Within-system neuroadaptations that contribute to the negative emotional state component of compulsivity
Under this conceptual framework, other within-system neuroadaptations would include increased sensitivity of receptor transduction mechanisms in the nucleus accumbens. Drugs of abuse have acute receptor actions that are linked to intracellular signaling pathways that may undergo adaptations with chronic treatment. Activation of adenylate cyclase, protein kinase A, cyclic adenosine monophosphate response-element binding protein (CREB), and ΔFosB has been observed during opioid withdrawal (Self et al., 1995; Shaw-Lutchman et al., 2002; Nye and Nestler, 1996; Nestler, 2004). The ΔFosB response is hypothesized to represent a neuroadaptive change that extends long into protracted abstinence (Nestler and Malenka, 2004).
