Long-term behavioral habituation (LTH), that is activity decrement upon repeated exposures to spatial novelty, is a relatively simple and ubiquitous form of behavioral plasticity in the animal kingdom, that can be used as a model of nonassociative learning in the freely behaving organism. Several strategies can be followed to tackle upon it. (a) Interference studies pertain to manipulation of the between-exposure interval by a variety of agents of different nature, that are known to interfere with hypothesized ''consolidation process(es)'' in associative learning paradigms. This approach indicates that LTH is modulated by NMDA receptors, requires polysome aggregation and protein synthesis, a functioning neocortex and both slow wave and paradoxical sleep. Further, it is modulated by endogenously released or exogenously given vasopressin and is not affected by blockade of endogenous opioids, at least through the ''mu'' receptor type. Moreover, LTH is disrupted by bilateral, electrolytic lesion of the locus coeruleus, but it is only impaired by 6-OH-DA bilateral lesion of the dorsal noradrenergic bundle, and it is facilitated by electrolytic lesion of the medial septal nuclei. (b) Noninterference correlative studies: Individual differences in behavioral variables can be correlated to some components of the architecture of the hippocampus to reveal structure-function relationships. (c) Noninterference maturation studies pertain to the study of the maturation of LTH during postnatal development in a scaled-down Lat-maze in normally reared rats and in rats with deranged rate of body and brain growth by litter size technique, differential stimulation or by perinatal propylthiouracil-induced hypothyroidism. (d) Noninterference development studies pertain to the formation of LTH varying the between-exposure interval. It was studied in albino rats of a Sprague-Dawley, random-bred stock (NRB) and of the Naples High (NHE) and Low-Excitability (NLE) lines. The study was carried out during the light or the dark phase of a 12:12LD cycle, by retesting at different inter-exposure intervals. Multivariate analysis of variance showed significant effects of strain, inter-exposure interval and of postexposure sleep or wakefulness. Furthermore, analysis of the temporal pattern showed the formation of LTH to follow a non linear complex function. Further, behavioral habituation consists of emotional and cognitive components that can be separated across different approaches. In conclusion, long-term
