Animal studies stimulus generalization

Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65,74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74). 

The methods to investigate the specificity of behaviorally active compounds include spontaneous responses of untrained animals and discrimination tests, where a discriminated stimulus is substituted by another closely related compound to detect the degree of generalization from one stimulus to another. In field studies, the first is the method of choice. 

When an animal is allowed to move freely in a given environment, he will do so as a consequence of a number of factors, although we cannot identify them as precisely as we might describe the stimulus responsible for a scratch reflex. General or spontaneous motor activity may be studied in an environmoit that is not familiar to the subject. It is then called exploratory behaviour. A classical example is the open-field test, in which the movements and simple emotional manifestations of a rat in a circular space are observed and counted. One must be aware of the fact that an unfamiliar environment may induce reactions for which the tmn exploration is inappropriate. For example, depending upon the charactraistics of the species, illumination or noise level may have aversive propnties resulting in escape responses and the like. Drug effects will, of course, vary as a function of such factors. It is therefore necessary to analyse them systematically. 

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