Abstract It was previously reported that systemic administration of the nonselective opioid antagonist, naltrexone, induces Fos-like immunoreactivity (FLI) within the central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis (lateral–dorsal division; BSTLD), nucleus accumbens shell (NACshell) and ventral tegmental area (VTA) of free-feeding rats. These findings suggest that cellular activity in these brain regions is subject to opioid-mediated inhibitory control under basal conditions. Considering the involvement of mesoaccumbens dopamine neurons and components of the `extended amygdala' in motivated behavior and reward, it was hypothesized that the induction of c-Fos by naltrexone accounts for the motivational-affective consequences of opioid antagonism. In Experiment 1, naltrexone was administered intracerebroventricularly (i.c.v.; 100 μg) to determine whether results obtained in the prior immunohistochemical studies could be attributed to blockade of opioid receptors in brain as opposed to peripheral tissues that convey visceral sensory inputs to the CeA and BSTLD. Naltrexone produced a marked increase in FLI within the CeA and BSTLD, and a moderate increase in NACshell. In Experiment 2, the κ opioid antagonist, nor-binaltorphimine (Nor-BNI; 20.0 μg, i.c.v.) reproduced the effect of naltrexone in BSTLD and CeA, suggesting that the induction of c-Fos in these two structures is a consequence of κ receptor blockade. The selective μ antagonist, CTAP (2.0 μg, i.c.v.), reproduced the effect of naltrexone in NACshell, suggesting that the induction of c-Fos in this structure is a consequence of μ receptor blockade. The functional implications of these results are discussed in terms of the known functions of these brain regions and opioid receptor types, and the prior observation that chronic food restriction eliminates the FLI induced by naltrexone in CeA and BSTLD. It is suggested that tonic μ opioid-mediated inhibition in NACshell has a predisposing effect on goal–approach behavior in general while κ opioid-mediated inhibition in CeA and BSTLD has a predisposing effect on palatability-driven feeding in particular. Finally, a possible relationship between food restriction-induced suppression of the κ opioid mechanism in CeA/BSTLD, local CRH function, and sensitization of the neural substrate for incentive-motivating effects of abused drugs is discussed.