Median raphe nucleus mediates forming long-term but not short-term contextual fear conditioning in rats

Melik, Enver; Babar-Melik, Emine; Özgünen, Tuncay; Binokay, Seçil

doi:10.1016/s0166-4328(00)00175-3

Cited by 24 publications

(16 citation statements)

References 33 publications

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“…These sections were assessed for tissue lesion in the MRN and for location of the tip of the guide cannulae in the dorsal hippo- campus. As shown previously, ibotenic acid at the dose used resulted in marked polygonal cell body loss in the MRN regions (26). The ventral positions of the tips of the guide cannulae ranged approximately from 2.0 to 2.3 mm (Figure 1), indicating that the infusion cannulae were positioned between 3.0-3.3 mm, i.e., in the dentate gyrus at the time of infusion.…”

Section: Histologysupporting

confidence: 63%

“…The lack of effect of MRN lesions on non-mnemonic index such as escape latency clearly indicated that the effect of lesions on scopolamine-induced working memory deficits was not due to the increased locomotor activity. Earlier, we showed that ibotenic MRN lesions had no effect on innate one-way escape latency (25) or on immediate freezing conditioning (26). It is important to note that MRN lesions did not alter response latencies in the vehicletreated animals, an effect that precluded the alteration in footshock sensitivity as a cause of deeper working memory deficits seen in the MRN-lesioned rats under the influence of the drug.…”

Section: Discussionmentioning

confidence: 66%

“…Each rat was placed in a stereotaxic frame under sodium pentobarbital anesthesia (45 mg/kg, ip) and 2 µl of ibotenic acid (1 µg/µl, Sigma I2765, St. Louis, MO, USA) or artificial cerebrospinal fluid (aCSF) (in sham-lesioned rats) was infused through a stainless steel infusion cannula (24 gauge) into the MRN region, as described previously (26). In the same rats, guide cannulae (21 gauge) were implanted bilaterally into the dorsal hippocampus 1 mm above the dentate gyrus for microinfusion of the drug.…”

Section: Surgerymentioning

confidence: 99%

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Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

Babar

Melik

Özgünen

2002

Braz J Med Biol Res

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The interactions between the median raphe nucleus (MRN) serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 µg/ side) produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus. Correspondence

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Section: Histologysupporting

confidence: 63%

Section: Discussionmentioning

confidence: 66%

Section: Surgerymentioning

confidence: 99%

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Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

Babar

Melik

Özgünen

2002

Braz J Med Biol Res

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“…However, there was no sign that the size of this effect was greater in the TÀ compared to the T+ volunteers. This result may seem surprising in view of serotonin's proposed role in the modulation of anxiety (Deakin and Graeff, 1991;Gray, 1987;Iversen, 1984), and the specific proposal that serotonergic activity mediates anticipatory anxiety states activated by aversive stimuli (Deakin and Graeff, 1991;Melik et al, 2000;Tye et al, 1977;Wilkinson et al, 1995). Of course, the involvement of serotonin in mediating anxiety remains controversial with, for example, continuing difficulties in demonstrating impaired conditioning to discrete stimuli as opposed to contextual stimuli following serotonin depletions (Mansbach and Geyer, 1988;Wilkinson et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Tryptophan Depletion Alters the Decision-Making of Healthy Volunteers through Altered Processing of Reward Cues

Rogers

Tunbridge

Bhagwagar

et al. 2002

Neuropsychopharmacol

252

231

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While accumulating evidence suggests that effective real-life decision-making depends upon the functioning of the orbitofrontal cortex, much less is known about the involvement of the monoamine neurotransmitter systems and, in particular, serotonin. In the present study, we explored the impact of depleting the serotonin precursor, tryptophan, on human decision-making. Eighteen healthy volunteers consumed an amino-acid drink containing tryptophan and 18 healthy volunteers consumed an amino-acid drink without tryptophan, before choosing between simultaneously presented gambles, differing in the magnitude of expected gains (ie reward), the magnitude of expected losses (ie punishment), and the probabilities with which these outcomes were delivered. Volunteers also chose between gambles probing identified non-nomative biases in human decision-making, namely, risk-aversion when choosing between gains and riskseeking when choosing between losses. Tryptophan-depleted volunteers showed reduced discrimination between magnitudes of expected gains associated with different choices. There was little evidence that tryptophan depletion was associated with altered discrimination between the magnitudes of expected losses, or altered discrimination between the relative probabilities with which these positive or negative outcomes were delivered. Risk-averse and risk-seeking biases were also unchanged. These results suggest that serotonin mediates decision-making in healthy volunteers by modulating the processing of reward cues, perhaps represented within the orbitofrontal cortex. It is possible that such a change in the cognition mediating human choice is one mechanism associated with the onset and maintenance of anhedonia and lowered mood in psychiatric illness.

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“…16 Pasif sakınma düzeneğinde, düzeneğin aydın-lık bölümünde sergilenen donma davranışı ise, çev-resel işaretlerin bir bölümüne karşı tetiklenen bilişsel tip korku şartlanmasının ölçütü olarak kabul edilmektedir. 30 Çalışmamızda BLA lezyonlu sıçanların anlık ve uzun süreli bellek testlerinde, düzeneğin aydınlık bölümünde sergiledikleri şartlı donma davranışı azalmıştır. Vazdarjanova ve ark., Y-kollu düzenekte tek bir kolda şok uyguladıktan sonra tüm düzenekte sergilenen donma davranışı-nın BLA lezyonunda bozulduğunu göstermişleri-dir.…”

Section: Pasi̇f Sakinma Düzeneği̇nde Anlik Ve Uzun Süreli̇ şArtli Korku unclassified

Role of Basolateral Amygdala in Formation of Anxiety Related Memory

Akkurt¹,

Kocahan²,

Melik³

et al. 2012

Turkiye Klinikleri J Med Sci

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Ö ÖZ ZE ET T A Am ma aç ç: : Amigdala kompleksi duygulanımda kritik rol oynamakta, anksiyete bozuklukları ve anksiyete ile ilişkili çevresel korku şartlanmasına katılmaktadır. Bu çalışmanın amacı kalıtsal anksiyete/korku davranışları ve öğrenilmiş bilişsel ve affektif anksiyete/korku davranışlarında bazolateral amigdala (BLA)'nın rolünün araştırılmasıdır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmamızda Wistar türü erkek sıçanlar kullanılmıştır. Denekler yalancı lezyonlu (kontrol) ve BLA lezyonlu olmak üzere iki gruba ayrılmıştır. Sıçanların cerrahi uygulamaya alındıktan sonra, 2 hafta iyileşmesine izin verilmiş, testleri bunun ardından yapılmıştır. Pasif sakınma testi ve işaretsiz Pavlov tipi korku şartlanması gibi öğrenme testleri kullanılarak BLA'nın kognitif ve affektif şartlı korku davranışlarının bellekte kazanımı, saklanması ve anımsanması üzerine etkisi değerlendirilmiştir. B Bu ul lg gu ul la ar r: : BLA lezyonlu sıçanlar, kontrol sıçanlarla karşılaştırıldığında pasif sakınma testinde, şoktan hemen ve 48 saat sonra, donma ve karanlıktan sakınma davranışlarında bozulma görülmüştür. Bu bulgu BLA lezyonunun bellekte kazanım ve kognitif korku şartlanma performansını bozduğunu göstermektedir. BLA lezyonu şok uygulanan çevrede (işaretsiz Pavlov tipi şartlanma düzeneği) tekrar test yapılması durumunda şartlı donmayı bozmuştur; bu bulgu, lezyonun affektif korku şartlanmasında kazanım ve saklama süreçlerini bozduğunu göstermektedir. S So on nu uç ç: : BLA'nın şartsız donma belleğinin ifadesine ve çevresel ipuçları ve şartsız uyaranın duysal bileşeni arasında ilişkisinin kurulmasına katıldığını ileri sürebiliriz.A An na ah ht ta ar r K Ke el li im me el le er r: : Amigdala; hafıza; korku; anksiyete A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Amygdala plays a critical role in affect, is involved in anxiety disorders and anxiety related environmental fear conditioning. The aim of this study was to investigate the role of basolateral amygdala (BLA) in hereditary anxiety/fear behaviours and learned cognitive and affective anxiety/fear behaviours. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Wistar male rats were used in our study. Subjects were divided into two groups as sham (control) group and BLA lesion group. Rats were allowed to heal for two weeks after surgical procedure and were tested thereafter. Effect of BLA on acquisition, storage and recalling of cognitive and affective fear behaviours was evaluated using learning tests like passive avoidance test and unsigned Pavlov type fear conditioning. R Re es su ul lt ts s: : In the passive avoidance test, immediately after and 48 hours after the shock, impairment was seen in freeze and avoidance from dark behaviors in rats with BLA lesions compared to control rats. This finding indicates that acquisition and cognitive fear conditioning performance in memory was impaired. When the test in the shock applied environment (unsigned Pavlov type conditioning mechanism) was repeated, BLA lesion impaired conditional freeze; this ...

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Median raphe nucleus mediates forming long-term but not short-term contextual fear conditioning in rats

Cited by 24 publications

References 33 publications

Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

Tryptophan Depletion Alters the Decision-Making of Healthy Volunteers through Altered Processing of Reward Cues

Role of Basolateral Amygdala in Formation of Anxiety Related Memory

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