Central Actions of Opiates and Opioid Peptides

Abstract

The in vivo study of opiates and opioid peptides is complicated by the multiple receptor affinities of the drugs presently available (Wood et al., 1981b; Wood, 1982a; Wood, 1983a). This property of the majority of compounds available for study demands that both extensive dose—response studies and naloxone reversibility be performed. If possible, stereospecificity for both the agonist actions and the reversal by an antagonist should be examined (Wood et al., 1984b). A further complication is also evident; namely, species differences that appear to be dependent upon species differences in the proportion of mu, delta, and kappa receptors in a brain area (Gillan and Kosterlitz, 1982; Wood, 1983a,b; Frischknecht et al., 1983) and in the proportion of pre-synaptic to postsynaptic opioid receptors on a given neuronal population (Wood and Richard, 1982). Multiple receptor types on the same neuron may be a further complication; however, the problems of receptor dualism via separate neuronal populations have been clearly demonstrated (Wood et al., 1983a). In this example, the Ag/Ant butorphanol, which possesses a bell-shaped dose—response curve with regard to increases in striatal dopamine metabolites, has an initial agonist action directly on dopamine neurons that is subsequently antagonized by another receptor action at a neuronal population caudal to the substantia nigra (Wood et al., 1983a).