Background While considerable evidence implicates DA D1-receptor signaling in the nucleus accumbens in motivation for cocaine during early stages of addiction, less is known regarding its role following the development of addiction. Here, we examined its role in the development of an addicted phenotype in intact male and female rats, and in female rats that were either resistant or vulnerable to developing this phenotype. Methods Intact males, females, and ovariectomized (OVX) females with and without estradiol (vulnerable, OVX+E; resistant, OVX+Veh) were given either short access (ShA; 3 fixed-ratio 1 sessions, maximum of 20 infusions) or 24-hr extended access (ExA) to cocaine for 10 days (4 trials/hr). Motivation for cocaine was assessed following a 14-day abstinence period using a progressive-ratio schedule. Once responding stabilized, the effects of intra-accumbens infusion of the D1-receptor antagonist, SCH-23390 (0, 0.3, 1.0, 3.0 μg), were examined. Results Motivation for cocaine was markedly higher following abstinence from ExA versus ShA self-administration in intact males and females, indicating the development of an addicted phenotype in these groups. Motivation for cocaine was also higher than ShA controls in OVX+E, but not OVX+Veh females following ExA self-administration, confirming the categorization of these groups as vulnerable versus resistant. Following ExA self-administration, intact males and females and OVX+E, but not OVX+Veh females, were less sensitive to the effects of D1-receptor antagonism as compared to their ShA counterparts. Conclusions These results suggest that the role of D1-receptor signaling, though critical in “non-addicted” stages, becomes diminished once addiction has developed.

In 2015, a multidisciplinary task force comprising pulmonologists, rheumatologists, pathologists, and radiologists representing the European Respiratory Society and American Thoracic Society published a diagnostic classification schema for individuals with interstitial lung disease and autoimmune features who did not meet criteria for a defined connective tissue disease. The term interstitial pneumonia with autoimmune features (IPAF) was applied. Classification criteria are often nonspecific, but up to 90% of subjects with IPAF have serological evidence for autoimmunity (particularly (+) antinuclear antibodies). Distinguishing patients with IPAF from idiopathic pulmonary disorders may be difficult. The natural history and appropriate management of IPAF have not been clarified, as data are largely limited to retrospective studies. In this review, we discuss the salient clinical, serologic, histologic, and radiographic features of IPAF and discuss an approach to management.