The atypical antidepressant mirtazapine attenuates expression of morphine-induced place preference and motor sensitization

Steven M. Graves, Amanda L. Persons, Jennifer L. Riddle, T. Celeste Napier

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Opioid abuse and dependence remains prevalent despite having multiple FDA-approved medications to help maintain abstinence. Mirtazapine is an atypical antidepressant receiving attention for substance abuse pharmacotherapy, and its action includes alterations in monoaminergic transmission. As monoamines are indirectly altered by opioids, the current investigation assessed the ability of mirtazapine to ameliorate morphine-induced behaviors. Conditioned place preference (CPP) is a behavioral assay wherein a rewarding drug is paired with a distinct environmental context resulting in reward-related salience of cues through learning-related neuronal plasticity. A second behavioral assay involved motor sensitization (MSn), wherein repeated administration results in an enhanced motoric response to an acute challenge, also reflecting neuronal plasticity. Attenuation of CPP and/or MSn provides two behavioral measures to suggest therapeutic potential for addiction therapy, and the present study evaluated the effectiveness of mirtazapine to reduce both behaviors. To do so, morphine-induced CPP was established using an eight day conditioning paradigm, and expression of CPP was tested on day 10 following a 24 h or 30 min mirtazapine pretreatment. To determine if mirtazapine altered the expression of MSn, on day 11, rats received a pretreatment of mirtazapine, followed 30 min later by a challenge injection of morphine. Pretreatment with mirtazapine 24 h prior to the CPP test had no effect on CPP expression. In contrast, a 30 min pretreatment of mirtazapine attenuated the expression of both CPP and MSn. Collectively, these results indicate that mirtazapine may help to maintain abstinence in opioid dependent patients.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalBrain Research
StatePublished - Sep 7 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by USPHSGs DA05255 and DA015760 to TCN , and DA024923 to SMG and TCN . The authors thank Chang He for her technical assistance.


  • Antidepressant
  • Conditioned place preference
  • Morphine
  • Motor sensitization


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