Original Investigation


, Volume 177, Issue 1, pp 68-78

First online:

Individual differences in locomotor reactivity to a novel environment and sensitivity to opioid drugs in the rat. II. Agonist-induced antinociception and antagonist-induced suppression of fluid consumption

  • David A. WhiteAffiliated withDepartment of Pharmacology, Rollins Research Center, Emory University School of Medicine Email author 
  • , Mikhail KalinichevAffiliated withBehavioral Neurobiology, Schizophrenia and Bipolar Disorders Research, Psychiatry CEDD
  • , Stephen G. HoltzmanAffiliated withDepartment of Pharmacology, Rollins Research Center, Emory University School of Medicine

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In an animal model for vulnerability to drug abuse, rats that are more reactive to a novel environment (high responders, HRs) are more sensitive to behavioral effects of psychostimulants than are less reactive rats (low responders, LRs). In a companion article, we reported that HRs and LRs differ in sensitivity to morphine-induced locomotor sensitization.


We tested whether LRs and HRs also differ in sensitivity to opioid-induced antinociception and opioid antagonist-induced suppression of fluid consumption.


LRs and HRs were categorized based on motor responses to novelty during a 30-min session. Responses to nociceptive stimuli of varied intensities were measured using the tail-flick and hot-plate tests alone or following cumulative doses of morphine (1.0–12 mg/kg), buprenorphine (0.025–0.6 mg/kg), or etorphine (0.25–6.0 μg/kg). Potential changes in endogenous opioid-mediated reward systems were tested using naltrexone-induced (0.01–30 mg/kg) suppression of drinking either water following 24-h deprivation or sweetened condensed milk in a non-deprived state. These effects were further examined following 2 weeks of daily access to sweetened condensed milk.


At the lowest stimulus intensity tested, HRs had significantly shorter tail-flick response latencies than LRs. Additionally, HRs were less responsive to cumulative doses of morphine than LRs. There were no overall group differences in the hot-plate test. Following 2 weeks of daily access to sweetened condensed milk, HRs were more sensitive to naltrexone-induced suppression of consumption.


Under the proper conditions, differences in sensitivity to opioid drugs between HRs and LRs at least partially extend to antinociceptive and appetitive reward systems and are suggestive of more extensive differences in phenotype. As with the effects of repeated morphine exposure on locomotor activity, the effect of repeated exposure to appetitive reward associated with sweetened milk appears to be more robust in LRs than HRs.


Opioids Drinking Milk Water Locomotion Antinociception Hot-plate Tail-flick