Robert D. Hienz - US grants

The overall objective of the proposed research is to provide an experimental analysis of the effects of drugs of abuse on sensory and motor function in non-human primates. Animal psychophysical procedures will be employed to obtain quantitative assessments of drug-induced changes in the following aspects of sensory function: 1) absolute auditory thresholds; 2) absolute visual thresholds; 3) discrimination of synthetic speech sounds (steady-state vowels); and, when indicated, 4) auditory frequency-difference limens. For each of these aspects of sensory function, motor function will also be assessed by examining reaction times to each type of sensory stimulus employed. All experiments will be conducted using a standards reaction time procedure with non-restrained laboratory baboons. The proposed research will emphasize the effects of combinations of ethanol with both marijuana extract and its main constituent, delta-9-THC. Additionally, basic studies will also be conducted on the effects of acute administration of the opioid agonists, antagonists, and mixed agonist-antagonists. The results will provide normative data on the effects of drugs of abuse on sensory and motor function across a range of drug doses, and on the interaction effects of the two most commonly abused compounds, ethanol and marijuana. The study will also provide information relevant to drug scheduling and clinical evaluation of functional decrements produced by these compounds.

The overall objective of the proposed research is to provide an experimental analysis of the effects of cocaine on sensory and motor function in non-human primates. Animal psychophysical procedures will be employed to obtain quantitative assessments of the effects of cocaine on the following aspects of sensory function: 1) absolute auditory thresholds; 2) absolute visual thresholds; 3) the discrimination of auditory frequency differences; and 4) discrimination of synthetic speech sounds. For each of these aspects of sensory function, motor function will also be assessed by examining reaction times to each type of sensory stimulus employed. All experiments will be conducted using a standard reaction time procedure with non-restrained laboratory baboons. The proposed research will assess the effects of both acute and chronic cocaine dosing regimens on sensory/motor function, and will also examine the effects of doses of cocaine combined with other drugs of abuse (ethanol, delta-9-THC, pentobarbital). The results will provide basic data on the effects of cocaine on sensory and motor function across a range of drug doses, and on the interaction effects of cocaine with other common drugs of abuse. The study will also provide information relevant to drug scheduling and clinical evaluation of functional decrements produced by cocaine.

An understanding of the effects of drugs of abuse on many aspects of behavior necessitates an understanding of drug effects on the basic sensory and motor functions underlying such behavioral performances as well. In this regard, the present proposal will investigate the effects of opioid drugs on aspects of sensory and motor function in nonhuman primates. A combination of behavioral pharmacological and animal psychophysicaI research techniques will be used to provide behavioral assessments of the effects of both acute and chronic administrations of opioids on a) auditory and visual thresholds, b) reaction times for auditory and visual stimuli, and c) speech sound discriminations in baboons. We have previously characterized the effects of acute administrations of morphine, buprenorphine, and naloxone on such sensory/motor performance measures. The proposed research will build upon this previous work with a series of three studies. First, we will extend the assessment of the sensory/motor effects of opioids to the characterization of the effects of chronic administration of morphine and buprenorphine on sensory/motor function; this will include a redetermination of acute dose-effect functions of these drugs following their chronic dosing histories in order to examine the possible role of tolerance or sensitivity in opioid effects on sensory/motor function. Second, we will measure the effects of both acute and chronic administration of morphine and buprenorphine on the accuracy of performing speech sound discriminations, as preliminary data suggest that such discriminations may be more sensitive to opioid drug effects (e.g., morphine impairs the accuracy of vowel discriminations, but not auditory and visual threshold discriminations). Third, studies will be conducted to investigate differences in morphine's effects on sensory threshold versus speech sound discrimination performances. These latter studies will manipulate the nondrug level of stimulus control involved in these discriminations, and then measure morphine's effects on discrimination accuracy as a function of both the drug dose and the differing levels of stimulus control. This research will provide fundamental data of the effects of opioids on sensory and motor function across a range of doses, and will yield information relevant to the clinical implications of the sensory/motor effects of abused drugs (e.g., morphine) and clinically relevant drugs (e.g., buprenorphine).

animal welfare research; environmental stressor; Primates; quality of life; animal care; ethology; body physical activity; veterinary science; baboons; behavior test; mature animal; Macaca mulatta; data collection;

animal welfare research; monitoring device; quality of life; behavioral habituation /sensitization; ethology; longitudinal animal study; body physical activity; sleep; baboons; Macaca mulatta; mature animal; data collection; behavior test;

DESCRIPTION: (Applicant's Abstract) The goal of the present proposal is to provide an analysis of the effects of a major drug of abuse, cocaine, on basic aspects of perceptual and motor function in nonhuman primates. The proposed work focuses on an animal model of hearing that uses biologically relevant sounds (i.e., speech) containing acoustic features that are critical for the perception of sounds in general, and for the underlying neural processing of acoustic stimuli by the auditory nervous system. This proposal's aims are to employ the developed perceptual discrimination procedures as a model for precisely determining the nature of cocaine's effects on fundamental perceptual-motor processes, and to relate these effects to possible dopamine (DA) receptor subtypes. One set of experiments will employ specially-synthesized speech stimuli which will provide precise control over the difficulty of the discriminations, and also allow us to relate cocaine's effects to explicit changes in perceptual thresholds for detecting changes in the spectral characteristics of speech. In a second set of experiments, the specificity of cocaine's effects on speech perception will be examined by measuring cocaine's effects when simple tones are substituted for the spectrally complex speech stimuli. A third set of experiments will relate the effects of cocaine on speech perception and reaction times to current knowledge regarding DA receptor subtypes by examining whether other DA agonists (selective for both D1-type and D2/D3-type receptors) may also elicit cocaine's stimulant-like effects on reaction times, or its adverse effects on speech discriminations. A fourth set of experiments will determine whether cocaine-induced reductions in the accuracy of speech perception may be attributed to effects on memory. This research will provide fundamental data on cocaine's effects on perceptual and motor functions in nonhuman primates across a range of doses, and its likely mechanisms of action via the DA system. The research will yield information directly relevant to the clinical implications of the perceptual/motor effects of cocaine use.

The proposed research will explore the development of a laboratory animal model for the experimental analysis of both chronic, long-term drug use and HIV/AIDS. The nonhuman primate model to be explored will combine current oral drug dosing techniques with a well-defined simian immunodeficiency virus (SIV-macaque model of HIV/AIDS to investigate the viral, behavioral, and CNS consequences associated with chronic exposure to drugs of abuse, SIV viruses, and their combination. First, oral self-dosing techniques will be used to establish chronic morphine dependence in macaque monkeys, with morphine dependence being assessed and monitored via the recording of continuous telemetric data on body temperature and general activity, and via behavioral observations of drug dependence. Second, the effects of chronic morphine self-dosing on immune function will be concurrently evaluated by assessing immune function during the development of dependence, during chronic morphine dependence, and during periods of withdrawal (short-term abstinence and precipitate withdrawal). Third, the effects of morphine dependence on the disease process will be assessed by comparing all measures (body temperature, general activity, immune system function) in groups of morphine-dependent and drug-free animals throughout the course of SIV disease progression. The development of a nonhuman primate model for the investigation of the effects of both chronic drug administration and SIV disease will be an important tool in advancing the scientific understanding of the relationship between drug use and HIV/AIDS, and their consequences on cognitive/behavioral processes.

The proposed research will investigate a new animal model of the effects of abused drugs upon perceptual function. The model focuses upon the auditory perception of biologically relevant, species-specific communication signals in primates and will provide for experimental studies on perceptual processes within the broader context of the social communication systems of the savanna baboon, Papio cynocephalus. The proposed research will 1) extend the analysis of the effects of drugs of abuse on perceptual processes to the perception of species-specific communication signals in baboons, and 2) examine the effects of major drugs of abuse such as stimulants and anxiolytics on the perception of communication signals associated with differing motivational and social contexts (e.g., affiliative, aggressive, submissive). The use of well-established psychophysical procedures will provide for precise, quantitative assessments of drug effects on perceptual function, and digitally generated exemplars of actual baboon calls will be employed to provide for precise control of relevant acoustic features. One set of experiments will compare the similarities of the previously- demonstrated effects of drugs of abuse on perception of speech sounds with the effects of drugs of abuse on the perception of species-specific vocalizations. A second set of experiments will examine the relationship between a drug's perceptual effects and the type of social communication signal being discriminated. A third set of experiments will examine the relationship between a drug's perceptual effects and the social rank of the sender and receiver of the signal. This research will provide fundamental data on the effects of drugs of abuse on perceptual function in nonhuman primates, and on the perception of communication signals of motivational and/or social significance. This research will advance our understanding of factors which contribute to the abuse liability of widely abused drugs, and will yield information directly relevant to the clinical implications of the perceptual effects associated with the use and abuse of drugs.

DESCRIPTION (provided by applicant): The proposed research will investigate non-human primate vocal communication and it's possible biological and evolutionary relationships to human language. Laboratory studies will be conducted on how baboons recognize differences their own highly vowel-like "grunt" vocalizations, and the results contrasted with how humans perceive the same baboon vocalizations. The studies will focus on the perception of both natural and synthetic variants of the affiliative "grunt" calls of baboons, and will complement prior work on both vocal analyses and field studies of these same baboon grunt calls. One set of experiments will determine how baboons use the acoustic features of vowel-like grunt calls to recognize a vocalizer's sex, and to test for the relative importance of specific acoustic cues that are likely to be important in these discriminations. Experiments will examine, in both baboons and humans, the generalization of male/female grunt calls to new tokens, use synthetic grunts to test the relative importance of fundamental frequency (F0) and formant patterning in these discriminations, and measure discrimination thresholds for recognition of vocalizer sex. A second set of experiments will determine how baboons use the acoustic features of vowel-like grunt calls to recognize other individuals, and also test for the relative importance of specific acoustic cues (F0, formant spacing) that are likely to be important in these discriminations. A third set of experiments will determine how baboons categorize vowel-like grunts based on their functional significance (i.e., "move" versus "infant" grunts) in the face of acoustic variation related to the sex and individual identity of the vocalizer. Experiments will characterize discrimination and labeling functions for natural and synthetic "move" and "infant" grunts in both baboons and humans (as a control group) to determine whether these grunt types are perceived in a linguistic-like fashion. The proposed research will extend our knowledge of the acoustic communication abilities of baboons and their relationships to the evolution of human communication.

DESCRIPTION (provided by applicant): The proposed research will investigate non-human primate vocal communication and it's possible biological and evolutionary relationships to human language. Laboratory studies will be conducted on how baboons recognize differences their own highly vowel-like "grunt" vocalizations, and the results contrasted with how humans perceive the same baboon vocalizations. The studies will focus on the perception of both natural and synthetic variants of the affiliative "grunt" calls of baboons, and will complement prior work on both vocal analyses and field studies of these same baboon grunt calls. One set of experiments will determine how baboons use the acoustic features of vowel-like grunt calls to recognize a vocalizer's sex, and to test for the relative importance of specific acoustic cues that are likely to be important in these discriminations. Experiments will examine, in both baboons and humans, the generalization of male/female grunt calls to new tokens, use synthetic grunts to test the relative importance of fundamental frequency (F0) and formant patterning in these discriminations, and measure discrimination thresholds for recognition of vocalizer sex. A second set of experiments will determine how baboons use the acoustic features of vowel-like grunt calls to recognize other individuals, and also test for the relative importance of specific acoustic cues (F0, formant spacing) that are likely to be important in these discriminations. A third set of experiments will determine how baboons categorize vowel-like grunts based on their functional significance (i.e., "move" versus "infant" grunts) in the face of acoustic variation related to the sex and individual identity of the vocalizer. Experiments will characterize discrimination and labeling functions for natural and synthetic "move" and "infant" grunts in both baboons and humans (as a control group) to determine whether these grunt types are perceived in a linguistic-like fashion. The proposed research will extend our knowledge of the acoustic communication abilities of baboons and their relationships to the evolution of human communication.