Abstract
Dextrorphan is a noncompetitive blocker of N-methyl-D-aspartate (NMDA) receptors. Since NMDA blockers are known to reduce the locomotor stimulatory and toxic effects of cocaine, it was speculated that dextrorphan would attenuate cocaine-induced behavioral excitatory motor activity associated with and without mechanical perturbation of the brainstem.
Technique: Motor activity was recorded following dextrorphan and/or cocaine challenge in 25 SHR rats. Ten were naive subjects. Mini-osmotic pumps delivering cocaine (2.5 mg/0.49 ul/hr) were placed in 15 subjects, and infusion was halted after the third infusion day. On the fifth day either a dextrorphan (25 mg/kg, subcutaneous) or a dextrorphan and cocaine (40 mg/kg, intraperitoneal) challenge was done. Ten rats had bipolar electrode implants in the bilateral brainstem. Five were treated with DC current lesions in each of 12 days over a 3-week period. The effects of brainstem lesions on escape behavior were also evaluated in those five subjects.
Results: In the naive subjects, dextrorphan reduced motor activity (P=.0001), whereas combined cocaine and dextrorphan increased motor activity (P=0.04). In lesioned subjects, dextrorphan decreased motor activity (P=0.0001). In electrode implant subjects, combined dextrorphan and cocaine challenge decreased the motor activity (P=0.04). Hyperactivity in the electrode implant group was greater than in the lesioned subjects. Midbrain electrolytic lesions attenuated escape behavior. A variety of behaviors were produced by brainstem lesions.
Conclusions: Dextrorphan and brainstem lesions reduced motor hyperactivity and escape behavior. In electrode implant subjects dextrorphan counteracted the expected cocaine excitatory motor effects. Dextrorphan did not activate nor facilitate seizures.
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Lundien, M., Andy, O.J., Rockhold, R.W. et al. Dextrorphan effects on cocaine and brainstem perturbation. Integrative Physiological and Behavioral Science 31, 224–230 (1996). https://doi.org/10.1007/BF02691453
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DOI: https://doi.org/10.1007/BF02691453