Serotonin 5-HT1A receptor binding sites in the brain of the pigeon (Columba livia)

Abstract

Serotonin (5-HT) is a modulatory neurotransmitter that is involved in a variety of physiological and behavioral functions. In mammals, dysfunction of the serotonergic system has been linked to various diseases such as depression, schizophrenia, Alzheimer's disease, and eating disorders (Müller et al., 2007;Michelsen et al., 2008;Remington, 2008;Terry et al., 2008;Akimova et al., 2009;Polter and Li, 2010). In addition, growing evidence found in many species indicates that 5-HT modulates learning and memory (Jacobs and Azmitia, 1992;Winsauer et al., 1996; Meneses, 1999;Clarke et al., 2004; Meneses and PerezGarcia, 2007;Müller et al., 2007;Bert et al., 2008;Gasbarri et al., 2008;González-Burgos and Feria-Velasco, 2008;Sitaraman et al., 2008;Sambeth et al., 2009;Bari et al., 2010).Serotonin binds to multiple receptors (Hoyer et al., 2002;Green, 2006), which are widely distributed throughout the brain (Chalmers and Watson, 1991;Baumgarten and Grozdanovic, 1995;Barnes and Sharp, 1999;Riad et al., 2000). One of the most prominent is the 5-HT 1A receptor, which was first cloned and described by Fargin et al. (1988). The 5-HT 1A receptor belongs to the G protein coupled receptor superfamily and binds to a Gi/o protein (Innis and Aghajanian, 1987;Polter and Li, 2010). It displays a high affinity for 5-HT and occurs both pre-and postsynaptically (Hall et al., 1985;van Wijngaarden et al., 1990;Riad et al., 2000). As somatodendritic autoreceptors, 5-HT 1A receptors modulate the activity of 5-HT neurons, whereas they modify neuronal activity in terminal areas as postsynaptic receptors (Müller et al., 2007).The distribution of 5-HT 1A receptors in the brain has been investigated by several methods in rodents, nonhuman primates, and humans. Thereby, a high correlation between receptor binding with [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([ 3 H]-8-OH-DPAT) and 5-HT 1A mRNA densities has been shown (Chalmers and Watson, 1991;Pompeiano et al., 1992). High 5-HT 1A receptor densities were detected in the dorsal and median raphe nuclei and in areas of the limbic system such as the hippocampus, the lateral septum, the amygdala, as well as the entorhinal and cingulate cortices Zilles et al., 1985Zilles et al., , 2000Palacios et al., 1990;Yilmazer-Hanke et al., 2003). Moderate binding was detected in the olfactory bulb, the thalamus, hypothalamus, and several brain stem nuclei as well as neocortical areas. Low levels, or no binding, were reported in the basal ganglia and cerebellum (Gozlan et al., 1983;Marcinkiewicz et al., 1984;Zilles et al., 1985Zilles et al., , 2000Hall et al., 1997;Vergé et al., 1986;Albert et al., 1990;Palacios et al., 1990;Pompeiano et al., 1992;Khawaja, 1995; Kia et al., 1996a,b;Farde et al., 1997;Raurich et al., 1999;Hume et al., 2001;Maeda et al., 2001;Geyer et al., 2005;Palchaudhuri and Flügge, 2005;Eickhoff et al., 2007;Topic et al., 2007). 5-HT 1A receptors play a role in executive functions, anxiety related behavior, learning and reinforcement, feeding behavior, and locomotor activity (Zilles et al., 2...

Distribution of serotonin 5-HT 1A -binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons ( Columba livia )

“…The present data indicate that 5-HT 1ARs are densely concentrated in the brainstem and in the periventricular preoptichypothalamic areas of the pigeon brain, extending previous findings that these receptors are widely distributed in the pallial and pretectal/tectal regions in this species [33]. The radioligand [ 3 H]-8-OH-DPAT appeared to bind most strongly to post-and pre-synaptic 5-HT 1ARs ; DPAT is a highly specific 5-HT 1AR agonist [58,59,60] that has been used as a radioligand to determine the distribution of 5-HT 1ARs in various vertebrate species [61,27,54,[62][63][64][65].…”

“…The [ 3 H]8-OH-DPAT labeling patterns described here and by Herold and colleagues [33] are in line with the intense c-Fos labeling induced by 5-HT or DPAT ICV injection in these preoptichypothalamic periventricular regions and in the SL and the BNSTl. 5-HT injection increased the number of c-Fos+ cells in the parenchyma (PVN, BNSTl, SL, POM and POA) the circumventricular organs (PVO, SFO), which were, exception for the PVN, attenuated or abolished by drinking.…”

“…The 5-HT-binding sites of the 5-HT 1AR were labeled with [ 3 H] 8-OH-DPAT [51,52] according to a previously published standardized protocol [53,54,33], which consisted of three steps. (1) The samples were preincubated for 30 min (at RT) in buffer (170 mM Tris-HCl buffer containing 4 mM CaCl 2 and 0.01% ascorbic acid, pH 7.6) to remove endogenous ligands from the tissue; (2) The 5-HT binding sites were labeled via incubation in 1 nM [ 3 H]8-OH-DPAT in buffer for 60 min at room temperature in the presence or absence of 1 M 5-hydroxytryptamine as a displacer (non-specific binding or total binding, respectively).…”

“…In mammalian brains, a high density of 5-HT 1ARs was detected in 5-HTergic areas of the brainstem [26] and the forebrain, such as the cingulate and entorhinal cortices, the hippocampus, the amygdala, the septum, the thalamus and the hypothalamus [27][28][29][30][31][32]. An autoradiographic study using pigeons indicated moderate to high expression of binding sites to [ 3 H]8-OH-DPAT in forebrain regions including the nidopallium, the hyperpallium, the hippocampus, the basal ganglia, and the amygdala [33]. However, the distribution of these receptors in the brainstem and in periventricular areas, such as the hypothalamus, of birds remains unknown.…”

Normative database of the serotonergic system in healthy subjects using multi-tracer PET

“…The 5-HT 1A receptor is a G-protein-coupled receptor. Among the 5-HT1 receptors, 5-HT 1A is of special interest because it is the most widespread receptor type in the mammalian brain (Herold et al, 2012). It appears as somatodendritic autoreceptor on serotonin neurons in the raphe nuclei controlling serotonergic cell firing (Evans et al, 2008;Hajos et al, 2001) and as heteroreceptors in projection areas inhibiting postsynaptic cell firing (Fink and Gothert, 2007).…”