Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs

Singewald, Nicolas; Salchner, Peter; Sharp, Trevor

doi:10.1016/s0006-3223(02)01574-3

Cited by 302 publications

(241 citation statements)

References 42 publications

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“…Local infusion of a D1 receptor antagonist into the PFC blocked footshockinduced reinstatement suggesting that such reinstatement could result from enhanced dopaminergic activity in the PFC (Capriles et al, 2003). Yohimbine activates a number of brain regions that are also activated by footshock, including the nucleus accumbens, the VTA and the PFC (Funk et al, 2006;Singewald et al, 2003). This latter finding, coupled with the effectiveness of dopamine receptor blockade in the PFC to reverse footshock-induced reinstatement, is intriguing in light of the fact that Ro60-0175 reduces the stressinduced rise in extracellular dopamine in the PFC (Pozzi et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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Previously, we showed that the 5-HT 2C receptor agonist Ro60-0175 reduces cocaine self-administration, and the ability of cocaine to reinstate responding after extinction of drug-seeking behavior. The present experiments extended these findings further by determining whether the effects of Ro60-0175 on self-administration were sustained with repeated treatment, and whether Ro60-0175 altered reinstatement induced by the pharmacological stressor yohimbine, or by the context in which self-administration occurred. In Experiment 1, Ro60-0175 (1 mg/kg, s.c.) reduced cocaine (0.25 mg/infusion) self-administration maintained by a progressive ratio schedule. This reduction was sustained over eight daily injections. In Experiment 2, rats self-administered cocaine in daily 2 h sessions for 15 days on a FR1 schedule. Following extinction, yohimbine (1 mg/kg, i.p.) reinstated responding, and this effect was reduced dose dependently by Ro60-0175 (0.3-3 mg/kg, s.c.). In Experiment 3, rats were trained to respond for cocaine on a FR1 schedule in a distinct environmental context (A); responding was then extinguished in a different context (B). Reinstatement tests occurred in either context A or B.Responding was reinstated only when rats were tested in the original self-administration context (A). This reinstatement was reduced dose dependently by Ro60-0175. All effects of Ro60-0175 were blocked by the 5-HT 2C receptor antagonist SB242084. Thus, Ro60-0175, acting via 5-HT 2C receptors, reduces cocaine self-administration and cocaine-seeking triggered by a stressor and by drug-associated cues. The effects of Ro60-0175 do not exhibit tolerance within the 8-day test period. These results indicate that selective 5-HT 2C receptor agonists may be a useful pharmacological strategy for treatment of drug abuse.

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Section: Discussionmentioning

confidence: 99%

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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“…LS is a prime candidate for modulation of maternal defense by BDZs because it is associated with fear and anxiety (Numan and Insel, 2003;Pesold and Treit, 1996;Singewald et al, 2003) and previously has been hypothesized to be a critical site of negative regulation for maternal aggression (D'Anna et al, 2005;Gammie et al, 2004). For example, for three peptides that inhibit maternal aggression, CRF (Gammie et al, 2004), urocotin (Ucn) 1, and Ucn 3 (D' Anna et al, 2005), c-Fos activity in LS was elevated with treatment at the dose that impaired aggression.…”

Section: Discussionmentioning

confidence: 99%

GABA enhancement of maternal defense in mice: Possible neural correlates

Lee

Gammie

2007

Pharmacology Biochemistry and Behavior

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Previous studies have shown that low doses of GABA A receptor agonists facilitate maternal defense of offspring (maternal aggression), without significantly affecting other maternal behaviors. In addition, it has been demonstrated that endogenous changes in GABAergic neurotransmission occur in association with lactation. This study investigated the effects of GABA A receptor agonist, chlordiazepoxide (CDP), a benzodiazepine (BDZ), on maternal behaviors including aggression, and identified brain regions with altered activity in association with treatment. Another aim of the study was to determine whether CDP injections could prevent decreases in maternal aggression that occur with pup separation. Intraperitoneal injections of 1mg/kg of CDP significantly increased maternal defense without affecting other maternal behaviors, although a trend towards elevated nursing was noted. CDP significantly reduced c-Fos in lateral septum (LS) and caudal periaqueductal gray (cPAG) in behaviorally-experienced mice relative to vehicle-injected controls. In behaviorally-naïve subjects, CDP also decreased c-Fos in LS, but in cPAG this decrease was just above significance (p = 0.051). CDP was not sufficient to "rescue" maternal aggression when pup stimulus was removed. Overall, these studies provide further insights into the role for GABA in maternal behaviors, including aggression, and how and where BDZs may act to modulate behavior.

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“…Brain regions analyzed for the number of c-Fos-ir nuclei were chosen based on previous studies implicating them in fear circuitry (Singewald and Sharp, 2000;Singewald et al, 2003) and central autonomic and/or osmotic regulation (see reviews (Johnson and Gross, 1993;Dampney, 1994)). Analysis of the number of c-Fos-ir nuclei in all brain regions analyzed using two-factor ANOVA with repeated measures revealed a lactate (F (1,19) …”

Section: Experiments 1: Cellular Responses In L-or D-ag Rats Followingmentioning

confidence: 99%

Neural Pathways Underlying Lactate-Induced Panic

Johnson

Truitt

Fitz

et al. 2007

Neuropsychopharmacol

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Panic disorder is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as 0.5 M sodium lactate infusions. Although studied for four decades, the mechanism of lactate sensitivity in panic disorder has not been understood. The dorsomedial hypothalamus/perifornical region (DMH/PeF) coordinates rapid mobilization of behavioral, autonomic, respiratory and endocrine responses to stress, and rats with disrupted GABA inhibition in the DMH/PeF exhibit panic-like responses to lactate, similar to panic disorder patients. Utilizing a variety of anatomical and pharmacological methods, we provide evidence that lactate, via osmosensitive periventricular pathways, activates neurons in the compromised DMH/PeF, which relays this signal to forebrain limbic structures such as the bed nucleus of the stria terminalis to mediate anxiety responses, and specific brainstem sympathetic and parasympathetic pathways to mediate the respiratory and cardiovascular components of the panic-like response. Acutely restoring local GABAergic tone in the DMH/PeF blocked lactate-induced panic-like responses. Autonomic panic-like responses appear to be a result of DMH/PeF-mediated mobilization of sympathetic responses (verified with atenolol) and resetting of the parasympathetically mediated baroreflex. Based on our findings, DMH/PeF efferent targets such as the C1 adrenergic neurons, paraventricular hypothalamus, and the central amygdala are implicated in sympathetic mobilization; the nucleus of the solitary tract is implicated in baroreflex resetting; and the parabrachial nucleus is implicated in respiratory responses. These results elucidate neural circuits underlying lactate-induced panic-like responses and the involvement of both sympathetic and parasympathetic systems.

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Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs

Cited by 302 publications

References 42 publications

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

GABA enhancement of maternal defense in mice: Possible neural correlates

Neural Pathways Underlying Lactate-Induced Panic

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