**1.1.The pineal gland**

The pineal gland, which is called as "seat of the rational soul" by Descartes, is a pine shaped, unpaired organ located at the epithalamus of the brain. The invagination of the diencephalon develops the pineal gland and it is connected to the habenular commissure with a stalk. There is a close link between the pineal gland and the third ventricle of the brain and the area of the third ventricle receiving the pineal stalk is known as the pineal recess. The pineal gland has an endogenous, circadian(around 24 hours) rhythmic pattern in its metabolic and/or neural activity. The weight and the volume of the pineal gland show big differences within and between the species depending on the time of year, age and the physiological status of the animal. The volume of the pineal gland tends to increase in line with increasing body weight (Binkley, 1988).

The mammalian pineal is specialized for only secretion whereas fish and amphibian pineal glands acting as a photoreceptive organ and in reptiles and in birds, pineal gland is both receiving the light and has secretory function. In some birds and lower vertebrates, pineal gland also works as a rhythm generator but in mammals it is working in the coordination of rhythm physiology. In mammals, the rhythm generator is located in the suprachiasmatic nuclei of the hypothalamus (Refinetti et al, 1994). Some fish, amphibians and reptiles have a pineal gland with the two components, namely, the extracranial parietal organ and the intracranial pineal organ (Arendt, 1995).

The neuronal innervation of the pineal gland in lower vertebrates and mammals is not alike because of the lost of the efferent innervation during the phylogenesis in lower vertebrates.

© 2012 Karakas and Coskun, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Karakas and Coskun, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The post-ganglionic sympathetic fibers arising from the superior cervical ganglion innervates mainly pineal gland of the mammals. Postganglionic fibers reaching the pineal organ via the nervi conarii release norepinephrine at night. This neurotransmitter then activates adenylate cyclase, stimulating production of the second messenger cyclic adenosine monophosphate (cAMP), which accelerates melatonin synthesis. The vascular supply of the pineal gland is very rich. The arterial supply of the pineal gland is provided by the branches of the posterior choroidal arteries. There is also a well-developed internal capillary network in pineal gland (Quay, 1974).

Intraamygdalar Melatonin Administration and Pinealectomy Affect Anxiety Like Behavior and Spatial Memory 17

taken up by other cells is non enzymatical degraded when it scavenges hydroxyl radicals. 3) Also, melatonin in the blood rapidly escapes into other body fluids. 4) Finally, melatonin attaches to specific receptors or binding sites located at various locations in the organism

The melatonin receptors involved in mediating the effects of melatonin on the reproductive and endocrine systems are presumed to be those located in the pars tuberalis of the anterior pituitary gland (Stankov et al, 1991). These cells are in close proximity to the primary portal plexus and the terminals of the hypothalamic releasing hormone neurosecretory cells in the median eminence. Melatonin theoretically controls the release of substances, e.g., gonadotropins or other factors, that act in a paracrine manner in the nearby median eminence thereby regulating the release of the hypothalamic releasing hormones, e.g., gonadotropin releasing hormone (GnRH). In this manner melatonin can obviously regulate the functional status of the gonads and control the reproductive capability of an animal on a seasonal basis.

Melatonin modulates many physiological functions such as sleep, circadian, visual, cerebrovascular, reproductive, neuroendocrine, and neuroimmunological functions (Arendt, 2000; Wirz-Justice, 2001; Borjigin et al., 1999; Brzezinzki, 1997; Masana and Dubocovich, 2001; Vanecek, 1999; Hardeland et al., 2006). The amphilicity of the melatonin is allowing the molecule to enter any cell, compartment or body fluid (Poeggeler et al., 1994). In addition to physiological functions, melatonin influences the behavioural processes such as learning, stress, anxiety like behaviors, and depression (Krause and Dubocovich, 1990; Mantovani et al, 2003; Naranjo-Rodriguez et al., 2000; Loiseau et al., 2006). With regard to behavioural processes, melatonin binding sites have been found in the regions implicated in cognition and memory in the brain (Cardinalli et al., 1979; Weaver et al., 1989). The previous studies have shown that passive and active avoidance learning are affected by melatonin (Martini, 1971; Kovács et al., 1974). Melatonin that decreases recognition time, leads to a facilitation of short-term memory (Argyriou et al, 1998]. Taken together, these findings

Melatonin receptors represent saturation by the melatonin concentrations, which are close to physiologic nighttime melatonin levels. Because of this reason, these receptors show a dosage dependent activity. The sleep-promoting and activity-inhibiting effects of melatonin are provided by its low levels (e.g.,50 pg/mL in blood plasma) at the beginning of the night. However, the high levels of melatonin (e.g.,150 pg/mL in blood plasma) do not enhance these behavioral parameters. Some diurnal variations are also evident in the sensitivity of the melatonin receptors since melatonin receptors are more sensitive during the daytime when the time endogenous melatonin is not secreted. The circadian phase shifting effect of melatonin may be due to the enhanced sensitivity of melatonin receptors to melatonin in the morning or in the evening hours in response to small increases in melatonin secretion (Reppert, 1997).

Melatonin seems to produce anxiolytic (Naranjo-Rodriguez et al., 2000; Papp et al., 2000) effects. The effect of melatonin on anxiety is suggested to be mediated by central gamma

suggest the beneficial effect of melatonin on cognition and memory.

*1.2.2. The role of melatonin hormone on anxiety and learning performance* 

(Panke et al, 1979; Steinlechner, 1996).

## **1.2. Melatonin hormone**
