D1 dopamine / mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression, and a conditioned place preference procedure: assessment of therapeutic index in male Sprague Dawley rats
Rationale and objectives: In vivo receptor interactions vary as a function of behavioral endpoint, with key differences between reflexive and non-reflexive measures that assess the motivational aspects of pain and pain relief. There have been no assessments of D1 dopamine agonist / mu opioid recepto...
| Published in: | Psychopharmacology Vol. 242; no. 4; pp. 751 - 763 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
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Springer Nature
Apr2025
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=183536978&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 183536978 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Apr2025 vid: 242 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 183536978 182316636 10.1007/s00213-025-06743-9 183536978 ppf: 751 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: D1 dopamine / mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression, and a conditioned place preference procedure: assessment of therapeutic index in male Sprague Dawley rats aug: au: LaCourse, Hannah Bennett, Lily Falstad, April Asmus, Francesca Smith, Meghan Davis, Ravin Harrington, Kylee Giuvelis, Denise King, Tamara Stevenson, Glenn W. affil: https://ror.org/02n2ava60 Department of Psychology, University of New England, Biddeford, ME, USA sug: ab: Rationale and objectives: In vivo receptor interactions vary as a function of behavioral endpoint, with key differences between reflexive and non-reflexive measures that assess the motivational aspects of pain and pain relief. There have been no assessments of D1 dopamine agonist / mu opioid receptor (MOR) agonist interactions in non-reflexive behavioral measures of pain. We examined the hypothesis that D1/MOR mixtures show enhanced effectiveness in blocking pain depressed behaviors while showing decreased side effects such as sedation and drug reward. Methods: SKF82958 and methadone were used as selective/high efficacy D1 and mu agonists, respectively. An FR10 operant schedule was utilized in the presence and absence of a lactic acid inflammatory pain-like manipulation, to measure antinociceptive and operant-rate-suppressing effects, respectively. Rewarding properties of the drug combinations were determined using a conditioned place preference procedure. Results: Methadone alone, but not SKF82958 alone, produced dose-dependent restoration of pain-depressed responding. Both SKF82958 and methadone produced dose-dependent response rate suppression. Three fixed proportion mixtures, based on the relative potencies of the drugs in the rate suppression assay, produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that the 0.17:1 mixture produced supra-additive antinociception and additive sedation. The 0.055:1 mixture produced additive antinociception with sub-additive sedation, and the 0.018:1 mixture had the highest therapeutic index (TI) relative to other mixtures and drugs alone. The antinociceptive doses and component doses for the 0.018:1 mixture did not produce conditioned place preference. Conclusions: These results suggest that D1-selective dopamine agonists may have utility as candidate opioid-sparing analgesics. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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