Differential expression of 5HT‐1A, α1b adrenergic, CRF‐R1, and CRF‐R2 receptor mRNA in serotonergic, γ‐aminobutyric acidergic, and catecholaminergic cells of the rat dorsal raphe nucleus

摘要: The dorsal raphe nucleus (DR) contains the highest concentration of serotonin neurons in brain and has extensive ascending projections that innervate most forebrain structures (Steinbusch, 1981). These projection have been shown to regulate a wide variety physiological responses behaviors, including sleep–wake states, feeding, nociception, neuroendocrine responses, motor activities (Jacobs Azmitia, 1992). In addition, increasing evidence implicated affective conditions, such as depression anxiety (Kahn et al., 1988; Graeff 1996). However, DR is not homogeneous structure, classified into subpopulations according their electrophysiological properties behaving animals. For example, activity type I make up majority serotonergic correlated with degree behavioral arousal Fornal, 1999). contrast, firing rate small group II neurons, found at caudal interface median nucleus, does correlate changes or (Rasmussen 1984). Although substantial numbers contain serotonin, many other neurotransmitters are also present, γ-aminobutyric acid (GABA), dopamine, glutamate, corticotropin-releasing factor (CRF), distribution cellular neurochemical phenotypes varies across rostral-caudal extent (Gamrani 1979; Stratford Wirtshafter, 1990; Jacobs 1992; Commons 2003). both afferent efferent exhibit distinct topographic arrangement (Kohler Steinbusch, 1982; Van Bockstaele 1993; Peyron 1996, 1998). Together these observations consistent idea regions may subserve different functions. Experimental support for this recently obtained animal model learned helplessness. model, animals experience uncontrollable shock profile from control over can escape an equivalent shock, interference subsequent behavior (Overmier Seligman, 1967; Irwin 1980), increased conditioned fear (Osborne 1975), (Short Maier, 1993). Converging suggests expression helplessness following stressor requires activation DR, specifically, half interventions reduce prevent development and/or behaviors (Maier 1993, 1994, 1995; Maswood 1998; Grahn 1999; Greenwood Administration CRF caudal, but rostral, impeded manner similar stress (Hammack 2002). Furthermore, consequences exposure were prevented by administration receptor antagonist before Use more selective agonists antagonists revealed effects due CRF-R2 Consistent observation increases subpopulation cells (Lowry 2000). rostral mid-DR reportedly inhibited (Kirby 2000). Despite growing dorsal-ventral variations relatively little known about relative colocalization patterns receptors DR. present dual situ hybridization study was therefore carried out assess whether there difference mRNA encoding (types 1 2) determine they expressed serotonergic, GABAergic, catecholaminergic neurons. pattern α1b adrenergic (α1b ADR) determined, because noradrenergic afferents exert tonic excitatory effect on through α1 ADR mechanism (Baraban Aghajanian, 1980a,b, 1981; Yoshimura 1985), intra-DR prevents (Grahn 2002), subtype highly rat (Day 1997). Finally, 1A (5HT-1A) autoreceptor plays vital role direct inhibition (Sprouse 1987), its reverse enhancement conditioning produced inescapable 1995), nonserotonergic reported four levels, dorsal, ventral, lateral divisions described. differential observed provide additional functional organization.