Novel environment

Most of these models evaluate the effects of drugs on the behaviour of animals when they are exposed to a novel environment. Novelty normally reduces animals exploratory activity but established anti-anxiety drugs consistently increase exploration of, and approaches to, the novel stimulus and reduce the neophobic ( avoidance ) reaction. There are several examples of tests based on this principle (Table 19.2) but two that are widely used are the plus-maze and the social interaction tests. 

Histamine decarboxylase knockout mice are unable to produce histamine and these animals are unable to maintain wakefulness in a novel environment. Systemic or intraventricular administration of histamine or Hi receptor agonists induces wakefulness whereas systemic or intraventricular administration of Hi receptor antagonists induces sleep. Local administration of an H3 receptor agonist in the TMN induces sleep whereas local administration of an H3 receptor antagonist into the TMN induces wakefulness. 

Hue G Decker M., Solomon L, Rye D. (2003). Increased wakefulness and hyper-responsivity to novel environments in mice lacking functional dopamine D3 receptors. In Society for Neuroscience. 

There appear to be important exceptions to the rule that a decrease in the availability of 5-HT in the mesolimbic pathway leads to increases in locomotor and investigatory activity. In contrast to the dramatic and pervasive hyperactivity produced by electrolytic lesions of the median raphe, similar depletions of 5-HT following the neurotoxic dihydroxytryptamines produce relatively subtle effects that appear to be related to the environmental context in which the behavior is monitored. For instance, microinjections of 5,7-DHT into the median raphe had no effect on the level of activity in a novel environment, whereas the same animals were hyperactive in a familiar environment (54). 

Low doses of both indole and phenylethylamine hallucinogens potentiate the normal neophobia exhibited by rats placed into a novel environment, which typically results in an initial suppression of locomotion and investigation. These effects are extremely susceptible to the influences of ambient stimulation and handling. The action of hallucinogens on inhibitory 5-HT autoreceptors does not appear to be responsible for these effects. The relevance of either inhibitory or excitatory 5-HT receptors on target neurons to these effects of hallucinogens should be more thoroughly examined. 

As multicellular life forms reached a sufficient degree of complexity, they improved their physical separation from the water medium, allowing migration to land and continued evolution in novel environments. In terrestrial plants and animals, water is no longer both external and internal, but solely the internal milieu, the milieu interieur, in constant flux with the environment yet carefully separated from it Such, in a nutshell, is the biophysical role of water as a medium. 

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. 

The interlayer region of LDHs can provide a novel environment for photochemical reactions of guest molecules [201-204]. For example, Takagi et al. reported that the controlled photodimerization of a variety of unsaturated carboxylate species intercalated in the interlayer galleries of Mg/Al LDH could occur between the layers [203]. Syn head-to-head cyclodimers were selectively formed in the irradiation of intercalated cinnamate ions, whereas two isomers of syn head-to-head and syn head-to-taU cyclodimers were formed for the case of phenylethenylbenzoates. The product selectivity was shown to be controlled by the Mg/Al ratio of the host LDH, and hence the packing density of the anions in the interlayer region [204]. 

Fig. 1 Exploration pattern in a novel environment typically displayed by rodents. Placed in one corner of the environment, a rodent will first explore the protected area along the walls (thigmotaxis) before entering the unprotected area...

Among the most frequently used paradigms are tests for unconditioned anxiety that are thought to be indicative for human generahzed anxiety symptoms (Crawley 1999). In these tests, rodents usually are confronted with a novel environment or stimulus, and behavioral patterns related to anxiety (see Sect. 2.1.1) are measured. In the following, the most commonly used tests for unconditioned behavior will be briefly described. 

Fletcher PJ, Davies M (1990) Effects of 8-OH-DPAT, buspirone and ICS 205-930 on feeding in a novel environment comparison with chlordiazepoxide and FG 1742. Psychopharmacology (Berl) 102 301-308... 

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). 

Behavioral analyses revealed that the mice overexpressing CRH-BP exhibit increased locomotor activity in a novel environment (Burrows et al. 1998). In addition, a tendency towards decreased anxiety-related behavior was observed on the elevated plus maze, which would be in line with limited availabihty of free CRH due to enhanced binding by CRH-BP in these animals. 

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