Increased relapse to cocaine‐seeking in a genetic model for depression

Abstract

The greatest difficulty in treating cocaine addiction is the enormous rates of relapse, which occur despite immense negative consequences. Relapse risks are even greater in addicts with comorbid depression, perhaps because they use drugs to alleviate depressive symptoms. Only a few preclinical studies have examined this comorbidity, mostly exploring depressive-like effects following drug exposure. We examined rats from two different depression-like models: (a) chronic-mild-stress (CMS), which respond to antidepressant medications and (b) depressed-rat-line (DRL), a genetic model of selective breeding, which is less responsive to antidepressant medications.We tested addictive behaviors in a cocaine self-administration procedure, including the "conflict model," where drug-seeking and relapse encounter adverse consequences: an electrified grid in front of the drug-delivering lever. Following behavioral testing, we explored a potential association between behavioral outcomes and protein expression of brain-derived neurotrophic factor (BDNF). We found that DRL rats self-administer more cocaine compared with both CMS and controls, while CMS and control groups did not differ significantly. Notably, DRL but not CMS rats, displayed higher rates of relapse than controls, and expressed higher levels of BDNF in the prelimbic cortex (PLC). Potential translation of these results suggest that medication-resistant depressed patients tend to consume more drugs and are more susceptible to relapse. The increase in PLC BDNF levels is consistent with previous rat models of depression, and concomitantly, with its suggested role in promoting cocaine-seeking.

BDNF and Cortisol in the Diagnosis of Cocaine-Induced Depression

“…Another explanation could be the presence of untreated depression as a risk factor for CUD. In a study evaluating an animal model, depressed rats administered more cocaine than nondepressed ones showed higher concentrations of BDNF at the prelimbic cortex ( 48 ). In this regard, it should be noted that our participants were either abstinent or in remission from the last depressive episode.…”

Sleep Disturbance Alters Cocaine-Induced Locomotor Activity: Involvement of Striatal Neuroimmune and Dopamine Signaling

“…Chronic SDs may induce negative moods, such as irritation, anxiety, and depression, which are well-known factors that play critical roles in promoting craving and relapse of abusing drugs during the cycle of withdrawal [43][44][45]. One common test monitoring the depression-and anxiety-like behaviors is to determine the times spent in the central and peripheral area in the open field test (OPT) [46].…”