Effect of Inhibition of the Central Nucleus of the Amygdala and Drug Experience on the Regions Underlying Footshock-Induced Reinstatement of Morphine Seeking

2008 ◽  
Vol 36 (5) ◽  
pp. 992-1000 ◽  
Author(s):  
DY Ma ◽  
MY Xu ◽  
HC Yang ◽  
LZ Yang

This study assessed the effect of inhibition of the central nucleus of the amygdala (CeA) and drug experience on brain regions underlying footshock-induced reinstatement of morphine-seeking behaviour in rats. The difference in time spent in two chambers of a place-preference apparatus was used to measure morphine-conditioned place preference. Fos was measured as a marker of neuronal activation in the ventral bed nucleus of the stria terminalis (BNSTv) and ventral tegmental area (VTA). Footshock was found to enhance Fos expression in the BNSTv regardless of drug experience. In the VTA, morphine and footshock had an interactive effect on the increase in Fos expression. Inhibition of the CeA decreased Fos expression in the BNSTv regardless of drug experience, whereas in the VTA this effect only occurred in morphine-treated rats. These results suggest that drug experience has no differential effect on the BNSTv however morphine produces footshock sensitization in the VTA. CeA inhibition modulates the footshock-induced activity of these regions of the brain and attenuates reinstatement of drug seeking behaviour.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gabor Wittmann ◽  
Nicholas Cosentino ◽  
Ronald M Lechan

Abstract We have observed that following a fast, animals terminate their food intake within 2h after refeeding accompanied by a pattern of neuronal activation as identified by c-fos immunostaining that involves a number of brain regions associated with the regulation of food intake including the nucleus tractus solitarius (NTS), parabrachial nucleus (PBN), central nucleus of the amygdala (CEA), hypothalamic arcuate and paraventricular nuclei, and bed nucleus of the stria terminalis. We also observed striking c-fos activation in the posterior-lateral hypothalamus called the parasubthalamic nucleus or PSTN, raising the possibility that it may also be an important anorectic center in the brain. To establish how the PSTN is integrated into the CNS, we performed dual-label retrograde tract tracing studies to characterize whether refeeding-activated PSTN neurons project to one, or more than one target area in the CNS. Adult, Sprague-Dawley rats received dual stereotaxic injections of Alexa Fluor 488- and Alexa Fluor 555-conjugated cholera toxin β subunit (CTB; 0.1%, 0.5–1 µl volume) into the 1) PBN and NTS, 2) PBN and CEA and 3) NTS and CEA. After 7–12 days, the animals were fasted for 24 h and then given free access to food for 2 h before euthanasia by transcardial perfusion with 4% paraformaldehyde. Brains with successful dual injections were further processed for c-fos immunohistochemistry. The results showed that 26.5±3.8% of PSTN neurons projecting to the PBN also project to the CEA, and 34.6±7.6% of PSTN neurons that project to the CEA also project to the PBN. In addition, 20.2±2.7% of PSTN neurons that project to the PBN also project to the NTS, and 38.1±9.7% of PSTN neurons that project to the NTS also project to the PBN. Furthermore, 35.0±12.5% of PSTN neurons that project to the CEA project to the NTS and 37.1±4.0% of PSTN neurons that project to the NTS project to the CEA. Finally, up to 15% of the neurons with dual projections to the PBN and CEA contained c-fos after refeeding; up to 18% of the neurons with dual projections to the PBN and NTS contained c-fos; and up to 30% of neurons with dual projections to the NTS and CEA contained c-fos. We conclude that a large number of PSTN neurons have more than one projection site within the brain, thus the PSTN appears to have the capability of simultaneously communicating information about appetite to several, major feeding-related sites within the brain, presumably to terminate feeding.


2021 ◽  
Vol 7 (2) ◽  
pp. eabe5948
Author(s):  
Elva Fridjonsdottir ◽  
Reza Shariatgorji ◽  
Anna Nilsson ◽  
Theodosia Vallianatou ◽  
Luke R. Odell ◽  
...  

l-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.


Author(s):  
Louis J. G. Gooren

Transsexualism is the condition in which a person with apparently normal somatic sexual differentiation is convinced that he/she is actually a member of the opposite sex. It is associated with an irresistible urge to be hormonally and surgically adapted to that sex. Traditionally transsexualism has been conceptualized as a purely psychological phenomenon, but research on the brains of male-to-female transsexuals has found that the sexual differentiation of the brain—the bed nucleus of the stria terminalis (BSTC) and the hypothalamic uncinate nucleus—had followed a female pattern (1). This finding may lead to a concept of transsexualism as a form of intersex, where the sexual differentiation of the brain (which in mammals also undergoes sexual differentiation) is not consistent with the other variables of sex, such as chromosomal pattern, nature of the gonad and nature of internal/external genitalia. Thus it can be argued that transsexualism is a sexual differentiation disorder.


2008 ◽  
Vol 100 (6) ◽  
pp. 3429-3436 ◽  
Author(s):  
Frank Z. Nagy ◽  
Denis Paré

The amygdala and bed nucleus of the stria terminalis (BNST) are thought to subserve distinct functions, with the former mediating rapid fear responses to discrete sensory cues and the latter longer “anxiety-like” states in response to diffuse environmental contingencies. However, these structures are reciprocally connected and their projection sites overlap extensively. To shed light on the significance of BNST–amygdala connections, we compared the antidromic response latencies of BNST and central amygdala (CE) neurons to brain stem stimulation. Whereas the frequency distribution of latencies was unimodal in BNST neurons (∼10-ms mode), that of CE neurons was bimodal (∼10- and ∼30-ms modes). However, after stria terminalis (ST) lesions, only short-latency antidromic responses were observed, suggesting that CE axons with long conduction times course through the ST. Compared with the direct route, the ST greatly lengthens the path of CE axons to the brain stem, an apparently disadvantageous arrangement. Because BNST and CE share major excitatory basolateral amygdala (BL) inputs, lengthening the path of CE axons might allow synchronization of BNST and CE impulses to brain stem when activated by BL. To test this, we applied electrical BL stimuli and compared orthodromic response latencies in CE and BNST neurons. The latency difference between CE and BNST neurons to BL stimuli approximated that seen between the antidromic responses of BNST cells and CE neurons with long conduction times. These results point to a hitherto unsuspected level of temporal coordination between the inputs and outputs of CE and BNST neurons, supporting the idea of shared functions.


2000 ◽  
Vol 278 (5) ◽  
pp. R1267-R1274 ◽  
Author(s):  
Colleen M. Novak ◽  
Laura Smale ◽  
Antonio A. Nunez

Most mammals show daily rhythms in sleep and wakefulness controlled by the primary circadian pacemaker, the suprachiasmatic nucleus (SCN). Regardless of whether a species is diurnal or nocturnal, neural activity in the SCN and expression of the immediate-early gene product Fos increases during the light phase of the cycle. This study investigated daily patterns of Fos expression in brain areas outside the SCN in the diurnal rodent Arvicanthis niloticus. We specifically focused on regions related to sleep and arousal in animals kept on a 12:12-h light-dark cycle and killed at 1 and 5 h after both lights-on and lights-off. The ventrolateral preoptic area (VLPO), which contained cells immunopositive for galanin, showed a rhythm in Fos expression with a peak at zeitgeber time (ZT) 17 (with lights-on at ZT 0). Fos expression in the paraventricular thalamic nucleus (PVT) increased during the morning (ZT 1) but not the evening activity peak of these animals. No rhythm in Fos expression was found in the centromedial thalamic nucleus (CMT), but Fos expression in the CMT and PVT was positively correlated. A rhythm in Fos expression in the ventral tuberomammillary nucleus (VTM) was 180° out of phase with the rhythm in the VLPO. Furthermore, Fos production in histamine-immunoreactive neurons of the VTM cells increased at the light-dark transitions when A. niloticus show peaks of activity. The difference in the timing of the sleep-wake cycle in diurnal and nocturnal mammals may be due to changes in the daily pattern of activity in brain regions important in sleep and wakefulness such as the VLPO and the VTM.


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