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Effects of chronic mild stress on the development of drug dependence in rats

Papp, Mariusza; Gruca, Piotra; Lason-Tyburkiewicz, Magdalenaa; Litwa, Ewaa; Willner, Paulb

Behavioural Pharmacology:
doi: 10.1097/FBP.0000000000000046
Research Reports

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

Author Information

aBehavioural Pharmacology Laboratory, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

bDepartment of Psychology, University of Wales Swansea, Swansea, UK

Correspondence to Mariusz Papp, PhD, Behavioural Pharmacology Laboratory, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343 Krakow, Poland E-mail:

Received December 16, 2013

Accepted May 16, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins