Exploratory behavior novel environments

Similar to LSD and other monoamine hallucinogens, mescaline suppresses locomotor and exploratory behavior in novel environments (Wing et al. 1990). Also similar to LSD, tolerance develops to the behavioral effects of chronic doses of mescaline (Murray et al. 1977). Mescaline increases aggression in rat models (Sbordone et al. 1978) however, this is an elicited aggression (by electric shock) and does not necessarily generalize to human behavior. Increased aggression is not characteristic of humans using mescaline. 

Studies in mice with a targeted inactivation of other 5-HT receptor sub-types, such as the S-HTsa and 5-HT7, or a transgenic line that overexpresses 5-HT3, demonstrate that these receptors modulate the activity of neural circuits involved specifically in exploratory and reward-related behavior. When exposed to novel environments, KO mice lacking the S-HTsa exhibit increased exploratory activity and an attenuated stimulatory effect of lysergic acid diethylamide (LSD) on exploratory activity but no change in anxiety-related behavior (Grailhe et al. 1999), whereas S-HTy KO mice do not express any overt behavioral phenotype at all (Hedlund et al. 2003). 

The importance of ventral striatal DA in the locomotor response to psychostimulants was demonstrated by current classic studies showing that manipulating ventral striatal DA transmission by lesion (Kelly and Iversen, 1976) or local infusion of DA receptor antagonists impairs while local infusion of DA receptor agonists (Pijenburg et al., 1976) evokes forward locomotion and exploratory behavior in a novel environment. Subsequent studies have attempted to establish which one among the main subdivisions of the ventral striatum (NAc shell, NAc core, olfactory tubercle) could be responsible for this function. This issue, however, is highly controversial. 

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