, Volume 225, Issue 4, pp 791–801 | Cite as

Modification of the behavioral effects of morphine in rats by serotonin (5-HT)1A and 5-HT2A receptor agonists: antinociception, drug discrimination, and locomotor activity

  • Jun-Xu Li
  • Aparna P. Shah
  • Sunny K. Patel
  • Kenner C. Rice
  • Charles P. FranceEmail author
Original Investigation



Indirect-acting serotonin (5-HT) receptor agonists can enhance the antinociceptive effects of morphine; however, the specific 5-HT receptor subtype(s) mediating this enhancement is not established.


This study examined interactions between morphine and both 5-HT1A and 5-HT2A receptor agonists in rats using measures of antinociception (radiant heat tail flick and warm water tail withdrawal), drug discrimination (3.2 mg/kg morphine versus saline), and locomotion.


Male Sprague–Dawley rats (n = 7-8 per group) were used to examine the effects of morphine alone and in combination with DOM (5-HT2A agonist) and 8-OH-DPAT (5-HT1A agonist).


DOM did not modify antinociceptive or discriminative stimulus effects while modestly attenuating locomotor-stimulating effects of morphine; the effect of DOM (0.32 mg/kg) on morphine-induced locomotion was prevented by the 5-HT2A receptor-selective antagonist MDL 100907. In contrast, 8-OH-DPAT (0.032–0.32 mg/kg) fully attenuated the antinociceptive effects (both procedures), did not modify the discriminative stimulus effects, and enhanced (0.32 mg/kg) the locomotor-stimulating effects of morphine. These effects of 8-OH-DPAT were prevented by the 5-HT1A receptor-selective antagonist WAY100635.


Agonists acting at 5-HT1A or 5-HT2A receptors do not modify all effects of mu opioid receptor agonists in a similar manner. Moreover, interactions between 5-HT and opioid receptor agonists vary significantly between rats and nonhuman primates, underscoring the value of comparing drug interactions across a broad range of conditions and in multiple species.


Serotonin receptor Rat Opioid Drug discrimination Antinociception Locomotor activity 



This study was supported, in part, by grants R01DA05018 and K0517918 (Senior Scientist Award to CPF). A portion of this work was supported by the Intramural Research Programs of National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism (KCR).

The authors would like to thank Christopher Cruz, Margarita Gardea, and Sonia Cano for their expert technical support.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Jun-Xu Li
    • 1
    • 4
  • Aparna P. Shah
    • 1
  • Sunny K. Patel
    • 1
  • Kenner C. Rice
    • 3
  • Charles P. France
    • 1
    • 2
    Email author
  1. 1.Department of PharmacologyUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  2. 2.Department of PsychiatryUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  3. 3.Chemical Biology Research Laboratory, Department of Health and Human ServicesNational Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH)BethesdaUSA
  4. 4.Department of Pharmacology and ToxicologyUniversity at Buffalo, The State University of New YorkBuffaloUSA

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