Nmda Receptors And The Development Of Tolerance To Other Behavioral Effects Of Opiates

In addition to analgesia, opiates produce a number of other physiological and behavioral effects. Tolerance may develop to some of these effects, but not to others. Moreover, an involovement of NMDA receptors in tolerance to opiate analgesia does not necessarily translate to an involvement of these receptors in tolerance to other opiate effects. In order to better understand the role of NMDA receptors in opiate-induced neural and behavioral plasticity, it is important to go beyond analgesia and explore the many other physiological and behavioral effects of opiates. Although not as extensive as the research on tolerance to opiate analgesia, work has begun on the role of NMDA receptors in tolerance to other effects of opiates, including temperature regulation, locomotor depression, suppression of operant responding, and discriminative stimulus effects (Table 3).

4.1 Temperature Regulation

The first systematic attempt to explore the role of NMDA receptors in tolerance to effects other than analgesia was reported by Bhargava and Matwyshyn (29). In these studies, morphine produced potent analgesia and an increase in body temperature (hyperthermia), and tolerance developed to both of these effects with chronic administration. MK-801 inhibited the development of tolerance to the analgesic effect, but not to the hyperthermic effect of morphine. Given that the two measures were made in the same animals, the dissociation between these effects is striking. These results suggest that although NMDA receptors are involved in the development of tolerance to some actions of opiates, their involvement may not be universal.

4.2. Locomotor Depression

Morphine produces robust effects on locomotion in laboratory rats. At lower doses, this is seen as a mild locomotor stimulation. At higher doses, a biphasic response emerges, with an initial depression of

Table 3

Inhibition of the Development of Tolerance to Effects of Opiates Other Than Analgesia by NMDA Receptor Antagonists

Table 3

Inhibition of the Development of Tolerance to Effects of Opiates Other Than Analgesia by NMDA Receptor Antagonists

NMDA receptor

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