Perceptual and motor effects of morphine and buprenorphine in baboons

Abstract

The effects of morphine and buprenorphine on auditory perceptual discriminations and response latency (“reaction time”) in baboons are compared. The task employed synthetic human vowel sounds that are readily generated in the laboratory, and closely approximate natural baboon “grunt” vocalizations [J. Acoust. Soc. Am. 101 (1997) 2951]. Baboons pressed a lever to produce one repeating “standard” vowel, and released the lever only when one of four other “comparison” vowels occasionally occurred in place of the standard vowel. The percentage of correct detections and median reaction time for each comparison were measured following intramuscular drug administrations of morphine (0.01–1.8 mg/kg) and buprenorphine (0.00032–0.032 mg/kg). Both morphine and buprenorphine impaired vowel discriminability, and greater impairments occurred for those comparison vowels that were more similar in formant structure to the standard vowel. Morphine increased reaction time in all baboons, and buprenorphine increased reaction time in two of three baboons. Morphine's perceptual effects occurred within 20–40 min following drug administration; buprenorphine's perceptual effects occurred 50–100 min following drug administration. Morphine and buprenorphine did not differ in the time course of their maximal reaction time effects. The results demonstrate that both morphine and buprenorphine can impair auditory discriminations involving human vowel sounds in baboons, as well as lengthen reaction times to the stimuli.

Introduction

Opioids have been shown to affect not only the perception of pain, but also perception in other modalities such as audition and vision. For example, morphine impairs the accuracy of rats in making both click and tone discriminations in the presence of background masking noise Hernandez and Appel, 1979, Koek and Slangen, 1983, in discriminating the position of a light flash (Grilly et al., 1980), and in acquiring conditioned responses to both tones and lights Schindler et al., 1984, Schindler et al., 1985. In pigeons, morphine impairs visual color discrimination accuracy West et al., 1982, Nielsen and Appel, 1983, and increases the percentage of errors in a repeated acquisition procedure (Thompson and Moerschbaecher, 1981). In general, these perceptual effects of morphine have been attributed to an effect on sensory or discrimination processes rather than changes in the organism's responsivity in the discrimination procedure (for review see Appel and Dykstra, 1977, Heise and Milar, 1984). Morphine-induced changes in perceptual function have not, however, been as readily demonstrated with nonhuman primates (for example, see Milar and Dykstra, 1985, Moerschbaecher et al., 1984, Moerschbaecher and Thompson, 1983, Samra et al., 1985), suggesting the possibility of a substantial species difference in morphine's effects on perceptual processes.

Research from this laboratory with baboons has also failed to demonstrate that either morphine or another common drug of abuse — cocaine — affects the detectability of simple tones or white light Spear et al., 1992, Hienz et al., 1993, Hienz et al., 1994. On the other hand, it has recently been shown that cocaine does impair the ability of baboons to perform another type of auditory discrimination — the discrimination of human speech sounds Hienz et al., 1995, Hienz et al., 1996. This result suggests the possibility that speech sound discriminations may be more susceptible to the effects of drugs than discriminations involving simple tones or white light, and that the use of speech sound discriminations may provide a better test of the possible perceptual effects of morphine.

There is evidence indicating that the discrimination of human speech sounds by nonhuman primates is a perceptual task more akin to those types of auditory discriminations made in the natural environment. First, there is a close resemblance between many human speech sounds and nonhuman primate vocalizations (Snowdon et al., 1982). Second, the acoustic properties of baboon grunt calls are extremely vowel-like, so much so that grunt calls have been referred to as “prototypical human vowel sounds” (Owren et al., 1997). Third, this acoustic similarity of baboon grunt calls to human vowels is paralleled by a functional similarity in the use of these types of signals in that (1) baboon grunts primarily cue individual identity; and (2) human vowel sounds also play a predominant role in cueing individual identity, while conveying relatively little linguistic information (Owren et al., 1997). Thus discriminations involving vowel sounds may not only be more sensitive indicators of drug effects as noted above, but also be more representative of discriminations of biological relevance for baboons.

The present experiment examined the effects of both morphine and buprenorphine upon speech sound discriminations in baboons. Buprenorphine was examined in the present study because previous research in this laboratory indicated differential sensory effects for buprenorphine and morphine in that buprenorphine raised thresholds for the detection of both auditory and visual stimuli in baboons, whereas morphine did not (Spear et al., 1992). Buprenorphine is a mixed agonist/antagonist that produces positive subjective reactions similar to that of morphine (Lukas et al., 1983), and has been a compound of great interest due to its ability to attenuate the subjective “high” effects of morphine (Bickel et al., 1987). Further, there has been interest in buprenorphine as a pharmacotherapy for abuse of both cocaine and heroin, since buprenorphine reduces self-administration of these drugs (e.g., Carroll and Lac, 1992, Carroll et al., 1992, Mello et al., 1989, Mello et al., 1990).