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Discrimination learning in oxycodone-treated nonhuman primates.
Drug Alcohol Depend 2019; 207:107778DA

Abstract

BACKGROUND

Prescription opioid abuse continues to be a public health concern of epidemic proportions. Notwithstanding the extensive literature regarding opioid action, there has been little systematic research regarding the effects of opioid dependence and withdrawal on aspects of cognition-related behavior in laboratory animals. The present studies examined the effects of the prescription opioid oxycodone on learning processes in nonhuman primates.

METHODS

The ability of subjects to repeatedly learn novel touchscreen-based visual discriminations was examined during three conditions of opioid exposure. Discrimination learning was examined, first, during oxycodone self-administration (3-hr sessions, 0.1 mg/kg/injection) and, next, during non-contingent chronic treatment with oxycodone (10 mg/kg/day). Finally, discrimination learning was re-examined during antagonist-precipitated opioid withdrawal (0.001-0.1 mg/kg naltrexone) and, subsequently, following abrupt discontinuation of oxycodone treatment.

RESULTS

Although motoric behavior was disrupted by oxycodone, neither the development of discrimination learning nor steady-state performance were impaired following oxycodone self-administration or during non-contingent chronic oxycodone treatment. However, discrimination learning was substantially impaired during oxycodone withdrawal, whether elicited by naltrexone or by abrupt oxycodone discontinuation. Moreover, these learning impairments were concordant with autonomic signs of opioid withdrawal.

CONCLUSIONS

Taken together, the present studies indicate that impairment of learning processes can accompany the unconditioned signs of opioid withdrawal.

Authors+Show Affiliations

Behavioral Biology Program, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.Behavioral Biology Program, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA.Behavioral Biology Program, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA.Behavioral Biology Program, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.Behavioral Biology Program, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA. Electronic address: bkangas@mclean.harvard.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31816487

Citation

Withey, Sarah L., et al. "Discrimination Learning in Oxycodone-treated Nonhuman Primates." Drug and Alcohol Dependence, vol. 207, 2019, p. 107778.
Withey SL, Doyle RJ, Porter EN, et al. Discrimination learning in oxycodone-treated nonhuman primates. Drug Alcohol Depend. 2019;207:107778.
Withey, S. L., Doyle, R. J., Porter, E. N., Bergman, J., & Kangas, B. D. (2019). Discrimination learning in oxycodone-treated nonhuman primates. Drug and Alcohol Dependence, 207, p. 107778. doi:10.1016/j.drugalcdep.2019.107778.
Withey SL, et al. Discrimination Learning in Oxycodone-treated Nonhuman Primates. Drug Alcohol Depend. 2019 Nov 27;207:107778. PubMed PMID: 31816487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discrimination learning in oxycodone-treated nonhuman primates. AU - Withey,Sarah L, AU - Doyle,Rachel J, AU - Porter,Erica N, AU - Bergman,Jack, AU - Kangas,Brian D, Y1 - 2019/11/27/ PY - 2019/09/16/received PY - 2019/11/25/revised PY - 2019/11/25/accepted PY - 2019/12/10/pubmed PY - 2019/12/10/medline PY - 2019/12/10/entrez KW - Cognition KW - Naltrexone KW - Nonhuman primate KW - Opioid KW - Oxycodone KW - Self-administration KW - Withdrawal SP - 107778 EP - 107778 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 207 N2 - BACKGROUND: Prescription opioid abuse continues to be a public health concern of epidemic proportions. Notwithstanding the extensive literature regarding opioid action, there has been little systematic research regarding the effects of opioid dependence and withdrawal on aspects of cognition-related behavior in laboratory animals. The present studies examined the effects of the prescription opioid oxycodone on learning processes in nonhuman primates. METHODS: The ability of subjects to repeatedly learn novel touchscreen-based visual discriminations was examined during three conditions of opioid exposure. Discrimination learning was examined, first, during oxycodone self-administration (3-hr sessions, 0.1 mg/kg/injection) and, next, during non-contingent chronic treatment with oxycodone (10 mg/kg/day). Finally, discrimination learning was re-examined during antagonist-precipitated opioid withdrawal (0.001-0.1 mg/kg naltrexone) and, subsequently, following abrupt discontinuation of oxycodone treatment. RESULTS: Although motoric behavior was disrupted by oxycodone, neither the development of discrimination learning nor steady-state performance were impaired following oxycodone self-administration or during non-contingent chronic oxycodone treatment. However, discrimination learning was substantially impaired during oxycodone withdrawal, whether elicited by naltrexone or by abrupt oxycodone discontinuation. Moreover, these learning impairments were concordant with autonomic signs of opioid withdrawal. CONCLUSIONS: Taken together, the present studies indicate that impairment of learning processes can accompany the unconditioned signs of opioid withdrawal. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/31816487/Discrimination_learning_in_oxycodone-treated_nonhuman_primates L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(19)30555-1 DB - PRIME DP - Unbound Medicine ER -