Aversive and Appetitive Events Evoke the Release of Corticotropin-Releasing Hormone and Bombesin-Like Peptides at the Central Nucleus of the Amygdala

Abstract

There is wide agreement that corticotropin-releasing hormone (CRH) systems within the brain are activated by stressful stimuli. There is also mounting evidence for the role of bombesin (BN)-like peptides in the mediation of the stress response. To date, however, the extent to which other stimuli increase the activity of these peptidergic systems has received little attention. In the present investigation we validated and used in vivo microdialysis sampling followed by ex vivo radioimmunoassays to monitor the release of CRH and BN-like peptides during appetitive (food intake) and stressful (restraint) events. It is demonstrated for the first time that the in vivo release of CRH and BN-like peptides at the central nucleus of the amygdala was markedly increased by both stressor exposure and food ingestion. In fact, the meal-elicited rise of CRH release was as great as that associated with 20 min of restraint stress. Paralleling these findings, circulating ACTH and corticosterone levels were also increased in response to both food intake and restraint. Contrary to the current views, these results indicate that either food ingestion is interpreted as a "stressful" event by certain neural circuits involving the central amygdala or that the CRH- and BN-related peptidergic systems may serve a much broader role than previously envisioned. Rather than evoking feelings of fear and anxiety, these systems may serve to draw attention to events or cues of biological significance, such as those associated with food availability as well as those posing a threat to survival.

Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat

“…For example, the role of CRH, released from terminals of hypothalamic PVN neurons, in mediating the neuroendocrine stress response has been established, 47,57,60 and local release of CRH in the ACe, influencing stress-induced behaviors, has been demonstrated. 40,54 Consistent with the functional role of hypothalamic and amygdala CRH in modulating stress responses, up-regulation of CRH expression in these two regions by challenges that activate the neuroendocrine stress response has been documented. 23,29 Teleologically, this mechanism for regulation of CRH levels should be advantageous, resulting in larger releasable pools of CRH upon subsequent challenges.…”

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

“…Corticosterone release is induced by experience with lever CS -food US paired sign-tracking procedures and is evident prior to the expression of sign-tracking CR performance. One possibility is that corticosterone induces a state of arousal (Merali et al, 1998; see also Killeen et al, 1978) that is conducive to the expression of sign-tracking CR performance (Tomie et al, 2002b(Tomie et al, , 2004b; moreover, higher levels of corticosterone are related to higher levels of alcohol drinking (Fahlke et al, 1994a, b) and the tendency to self-administer abused drugs (Piazza et al, 1989;Rouge-Pont et al, 1993;Lucas et al, 1998; for reviews see Piazza and Le Moal, 1996;Koob, 1999).…”

Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

“…It is also important to note that a growing body of evidence implicates the corticotropin-releasing factor (CRF) systems in the amygdala in anxiety responses. In fact, enhanced CRF release in the amygdala represents a mechanism underlying the anxiogenic and aversive consequences of withdrawal (Menard and Treit, 1999;Merali et al, 1998;Wiersma et al, 1995) common to drugs of abuse such as nicotine and ethanol (Merlo Pich et al, 1995;Rivier, 1996).…”