Aggression, anxiety and vocalizations in animals: GABA A and 5-HT anxiolytics

A continuing challenge for preclinical research on anxiolytic drugs is to capture the affective dimension that characterizes anxiety and aggression, either in their adaptive forms or when they become of clinical concern. Experimental protocols for the preclinical study of anxiolytic drugs typically involve the suppression of conditioned or unconditioned social and exploratory behavior (e.g., punished drinking or social interactions) and demonstrate the reversal of this behavioral suppression by drugs acting on the benzodiazepine-GABA A complex. Less frequently, aversive events engender increases in conditioned or unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear-potentiated startle). More recently, putative anxiolytics which target 5-HT receptor subtypes produced effects in these traditional protocols that often are not systematic and robust. We propose ethological studies of vocal expressions in rodents and primates during social confrontations, separation from social companions, or exposure to aversive environmental events as promising sources of information on the affective features of behavior. This approach focusses on vocal and other display behavior with clear functional validity and homology. Drugs with anxiolytic effects that act on the benzodiazepine-GABA A receptor complex and on 5-HT 1A receptors systematically and potently alter specific vocalizations in rodents and primates in a pharmacologically reversible manner; the specificity of these effects on vocalizations is evident due to the effectiveness of low doses that do not compromise other physiological and behavioral processes. Antagonists at the benzodiazepine receptor reverse the effects of full agonists on vocalizations, particularly when these occur in threatening, startling and distressing contexts. With the development of antagonists at 5-HT receptor subtypes, it can be anticipated that similar receptor-specificity can be established for the effects of 5-HT anxiolytics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46351/1/213_2005_Article_BF02245590.pd

Discrimination of Direction in Fast Frequency-Modulated Tones by Rats

Fast frequency modulations (FM) are an essential part of species-specific auditory signals in animals as well as in human speech. Major parameters characterizing non-periodic frequency modulations are the direction of frequency change in the FM sweep (upward/downward) and the sweep speed, i.e., the speed of frequency change. While it is well established that both parameters are represented in the mammalian central auditory pathway, their importance at the perceptual level in animals is unclear. We determined the ability of rats to discriminate between upward and downward modulated FM-tones as a function of sweep speed in a two-alternative-forced-choice-paradigm. Directional discrimination in logarithmic FM-sweeps was reduced with increasing sweep speed between 20 and 1,000 octaves/s following a psychometric function. Average threshold sweep speed for FM directional discrimination was 96 octaves/s. This upper limit of perceptual FM discrimination fits well the upper limit of preferred sweep speeds in auditory neurons and the upper limit of neuronal direction selectivity in the rat auditory cortex and midbrain, as it is found in the literature. Influences of additional stimulus parameters on FM discrimination were determined using an adaptive testing-procedure for efficient threshold estimation based on a maximum likelihood approach. Directional discrimination improved with extended FM sweep range between two and five octaves. Discrimination performance declined with increasing lower frequency boundary of FM sweeps, showing an especially strong deterioration when the boundary was raised from 2 to 4 kHz. This deterioration corresponds to a frequency-dependent decline in direction selectivity of FM-encoding neurons in the rat auditory cortex, as described in the literature. Taken together, by investigating directional discrimination of FM sweeps in the rat we found characteristics at the perceptual level that can be related to several aspects of FM encoding in the central auditory pathway