Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress.

Abstract

The effect of intracerebroventricular injection of the mitosis inhibitor colchicine and of immobilization stress, subcutaneous injection of capsaicin, and intraperitoneal injection of hypertonic salt solution on expression of c-Fos-like immunoreactivity was studied in the rat brain with immunohistochemistry. All the procedures induced c-Fos immunoreactivity in parvocellular neurons of the paraventricular nucleus, and many of these neurons also contained corticotropinreleasing factor immunoreactivity. c-Fos immunoreactivity was also observed, for example, in subpopulations of neurons in the locus coeruleus, the ventrolateral medulla oblongata, and the nucleus tractus solitarii. Many of these cells also expressed catecholamine-synthesizing enzymes. The results suggest that intraventricular injection of colchicine is a stressful stimulus and support the view that several catecholamine cell groups in the lower brainstem are part of the brain circuitry mediating stress reactions, as are the hypothalamic neurons that contain corticotropin-releasing factor.The c-fos gene (1, 2) is expressed in many tissues in response to growth factor stimulation (3-9). It has been suggested that induction of protooncogenes such as c-fos may be important in the establishment of prolonged functional changes in neurons (10). It has been demonstrated by immunohistochemical methods that various types of stimulation induce a c-Fos protein-like immunoreactivity in specific neuron populations in various brain regions (11)(12)(13). Thus, immunohistochemical analysis of expression of c-Fos protein in nervous tissue may represent a new tool in neurobiology for metabolic mapping at the cellular level (14). In fact, numerous papers based on this methodology have appeared during the last 2 years.In the present study we have used immunohistochemistry to analyze to what extent various stressors may induce expression of c-Fos-like immunoreactivity in certain brain regions. In addition, antisera to neuropeptides and transmitter-synthesizing enzymes were used to further characterize c-Fos-activated neurons. Of particular interest to us has been the question whether or not intracerebroventricular (i.c.v.) injections of the mitosis inhibitor colchicine (15) may affect stress-related systems. Ever since colchicine was shown to inhibit axonal transport (16,17) and to cause marked accumulation of amine storage granules in cell bodies (18), this drug has been used to improve histochemical visualization of transmitters, peptides, and related substances in neuronal cell bodies (19,20). Our results demonstrate that several stress-inducing procedures as well as i.c.v. colchicine treatment, including the i.c.v. injection procedure per se, cause expression of c-Fos protein in restricted neuronal cell populations both in the hypothalamus, including the corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus (PVN), and in the lower brainstem, particularly in catecholamine neurons. MATERIALS AND METHODSMale Sprague-Dawley rats (250...

Ventral pallidum self-stimulation induces stimulus dependent increase in c-fos expression in reward-related brain regions

“…Relevant to this hypothesis is the fact that animals learn to switch-off forced rewarding stimulation if a lever is made available to them 36 and that experimental stress induces measurable Fos-immunoreactivity. 6,10,41 In conclusion, rewarding electrical stimulation of the VP increased Fos immunoreactivity in a frequency-dependent manner in several brain structures known to participate in the regulation of drug and/or brain stimulation reward (PLH, NAC, LSI, VTA and mPFC), and failed to do so in structures devoid of such involvement (SNR and DL-STR). This finding, and the fact that Fos-immunoreactivity correlated with reward magnitude, but not with bar-pressing behaviour, suggests a reward-specific effect.…”

Differential Activation of the Periaqueductal Gray by Mild Anxiogenic Stress at Different Stages of the Estrous Cycle in Female Rats

“…During the initial assessment phase, determination of the emotional significance of a novel and hence inherently stressful stimulus is likely to occur in cortical and/or limbic regions, which then engage the PAG downstream to initiate and integrate the somatomotor and autonomic components of the animal's response. It is well established that mild psychogenic stress activates neurons in various cortical areas that project to the PAG (Beitz 1982;Ceccatelli et al, 1989; Cullinan et al, 1995; …”

Isolation rearing in the rat disrupts the hippocampal response to stress

“…The expression of immediate early genes indicates that the cell has been activated and thus might be due to direct activation by the stressors or modulation of a particular set of gene expressions to cope with the stress situation (Senba and Ueyama, 1997). Since the last decade c-fos has been used as a marker of neuronal activation in living animals after exposure to various kind of stimuli or stressors (Morgan et al, 1987;Sagar et al, 1988;Ceccatelli et al, 1989). Previous studies on restraint stress demonstrated a pattern of c-fos expression in the forebrain and brainstem (Ceccatelli et al, 1989;Schreiber et al, 1991;Arnold et al, 1992;Senba et al, 1993;Imaki et al, 1995;Stone and Zhang, 1995;Bonaz and Rivest, 1998).…”

“…Since the last decade c-fos has been used as a marker of neuronal activation in living animals after exposure to various kind of stimuli or stressors (Morgan et al, 1987;Sagar et al, 1988;Ceccatelli et al, 1989). Previous studies on restraint stress demonstrated a pattern of c-fos expression in the forebrain and brainstem (Ceccatelli et al, 1989;Schreiber et al, 1991;Arnold et al, 1992;Senba et al, 1993;Imaki et al, 1995;Stone and Zhang, 1995;Bonaz and Rivest, 1998). C-fos expression after restraint stress mainly occurs in the forebrain, including the lateral septum, medial preoptic area, median amygdala nucleus (AMe), parvocellular region of paraventricular hypothalamus and disparate cortical regions, with scattered cells found in the dorsal part of supraoptic nucleus.…”