Conditioned antinociception and freezing using electrical stimulation of the dorsal periaqueductal gray or inferior colliculus as unconditioned stimulus are differentially regulated by 5-HT2A receptors in rats

Castilho, V.M.; Brandão, Marcus Lira

doi:10.1007/s002130100697

Cited by 69 publications

(38 citation statements)

References 56 publications

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“…The pattern of results obtained in the present experiments parallels those from typical avoidanceescape procedures, which utilize electric shock as the UCS, for example, an auditory stimulus paired with foot shock elicits classical conditioned responses (LeDoux et al, 1986(LeDoux et al, , 1990. From the anatomo-functional viewpoint, the IC may be associated with the processing of aversive conditioned stimuli and, for extension, with conditioned fear Castilho and Brandão, 2001). Therefore, the present results are in line with recent evidence obtained in this laboratory that has shown that rats learn to avoid the IC stimulation when the warning stimulus is a light and not a tone (Troncoso et al, 1998).…”

Section: Discussionsupporting

confidence: 78%

“…Latent inhibition has been considered as a model for information filtering processesand demonstrates attentional processes in rats that are responsive to drug treatment in a fashion that parallels drug responses seen in humans with schizophrenia (Makintosh, 1975;Lubow et al, 1982;Dunn et al, 1993;Sandner et al, 2002). We have already shown that stimulation of neural circuits in the central nucleus of the IC supports Pavlovian conditioning and that latent inhibition may be demonstrated using stimulation of these neural circuits in the IC as negative reinforcement Troncoso et al, 1998;Castilho and Brandão, 2001).…”

Section: Introductionmentioning

confidence: 94%

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Apomorphine Enhances Conditioned Responses Induced by Aversive Stimulation of the Inferior Colliculus

Troncoso¹,

Osaki²,

Mason³

et al. 2003

Neuropsychopharmacol

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Consistent evidence has shown that learning may be produced in paradigms using electrical stimulation of the inferior colliculus (IC) as unconditioned stimulus (UCS). Recent reports have also demonstrated that aversive stimulation of the IC, at the escape threshold, enhances dopamine (DA) release in the prefrontal cortex. The purpose of the present study was to determine whether dopaminergic mechanisms are involved in the Pavlovian conditioning and latent inhibition using IC stimulation as UCS and light as conditioned stimulus (CS). Rats were placed inside a shuttle box and subjected to a two-way avoidance paradigm. IC aversive electrical stimulation was used as UCS and shuttle box illumination as CS. The rats quickly learned to avoid or interrupt the IC stimulation. Apomorphine injections produced a dose-dependent increase in the number of avoidance responses. On the other hand, chlorpromazine administration promoted a dose-dependent reduction of the avoidance responses. Previous injections of chlorpromazine inhibited the effects of apomorphine. Also, previous exposure to unreinforced light weakened the strength of the conditioning. Apomorphine blocked this latent inhibition effect, which was antagonized by previous injections of chlorpromazine. These findings bring evidence for the involvement of DA in the setting up of adaptive responses to aversive states generated at the IC level, which may underlie stressful situations present in anxiety.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 94%

Apomorphine Enhances Conditioned Responses Induced by Aversive Stimulation of the Inferior Colliculus

Troncoso¹,

Osaki²,

Mason³

et al. 2003

Neuropsychopharmacol

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“…A single electrical stimulation of the dPAG at the escape threshold does not lead to any context conditioning. In fact, at least two sessions of pairings of dPAG electrical stimulation environmental stimuli are required to produce contextual fear conditioning (Castilho et al 2001). …”

Section: Vianna Et Almentioning

confidence: 99%

Lesion of the Ventral Periaqueductal Gray Reduces Conditioned Fear but Does Not Change Freezing Induced by Stimulation of the Dorsal Periaqueductal Gray

Vianna¹,

Graeff²,

Landeira-Fernández³

et al. 2001

Learn. Mem.

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Previously-reported evidence showed that freezing to a context previously associated with footshock is impaired by lesion of the ventral periaqueductal gray (vPAG). It has also been shown that stepwise increase in the intensity of the electrical stimulation of the dorsal periaqueductal gray (dPAG) produces alertness, then freezing, and finally escape. These aversive responses are mimicked by microinjections of GABA receptor antagonists, such as bicuculline, or blockers of the glutamic acid decarboxylase (GAD), such as semicarbazide, into the dPAG. In this work, we examined whether the expression of these defensive responses could be the result of activation of ventral portion of the periaqueductal gray. Sham- or vPAG electrolytic–lesioned rats were implanted with an electrode in the dPAG for the determination of the thresholds of freezing and escape responses. The vPAG electrolytic lesions were behaviorally verified through a context-conditioned fear paradigm. Results indicated that lesion of the vPAG disrupted conditioned freezing response to contextual cues associated with footshocks but did not change the dPAG electrical stimulation for freezing and escape responses. In a second experiment, lesion of the vPAG also did not change the amount of freezing and escape behavior produced by microinjections of semicarbazide into the dPAG. These findings indicate that freezing and escape defensive responses induced by dPAG stimulation do not depend on the integrity of the vPAG. A discussion on different neural circuitries that might underlie different inhibitory and active defensive behavioral patterns that animals display during threatening situations is presented.

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“…Recently, it has been shown that 5-HT 2A receptors alone mediate fear and anxiety states (Castilho and Brandao, 2001;Weisstaub et al, 2006) and that activation of 5-HT 2A receptors improves learning and working memory (Williams et al, 2002;Harvey, 2003;Harvey et al, 2004;Romano et al, 2006). Also, 5-HT is involved in the control of both cardiovascular and acute psychological stress reactivity (Davies et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Serotonergic Modulation of Plasticity of the Auditory Cortex Elicited by Fear Conditioning

Suga²

2007

J. Neurosci.

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In the awake big brown bat, 30 min auditory fear conditioning elicits conditioned heart rate decrease and long-term best frequency (BF) shifts of cortical auditory neurons toward the frequency of the conditioned tone; 15 min conditioning elicits subthreshold cortical BF shifts that can be augmented by acetylcholine. The fear conditioning causes stress and an increase in the cortical serotonin (5-HT) level. Serotonergic neurons in the raphe nuclei associated with stress and fear project to the cerebral cortex and cholinergic basal forebrain. Recently, it has been shown that 5-HT 2A receptors are mostly expressed on pyramidal neurons and their activation improves learning and memory. We applied 5-HT, an agonist (␣-methyl-5-HT), or an antagonist (ritanserin) of 5-HT 2A receptors to the primary auditory cortex and discovered the following drug effects: (1) 5-HT had no effect on the conditioned heart rate change, although it reduced the auditory responses; (2) 4 mM 5-HT augmented the subthreshold BF shifts, whereas 20 mM 5-HT did not; (3) 20 mM 5-HT reduced the long-term BF shifts and changed them into short-term; (4) ␣-methyl-5-HT increased the auditory responses and augmented the subthreshold BF shifts as well as the long-term BF shifts; (5) in contrast, ritanserin reduced the auditory responses and reversed the direction of the BF shifts. Our data indicate that the BF shift can be modulated by serotonergic neurons that augment or reduce the BF shift or even reverse the direction of the BF shift. Therefore, not only the cholinergic system, but also the serotonergic system, plays an important role in cortical plasticity according to behavioral demands.

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Conditioned antinociception and freezing using electrical stimulation of the dorsal periaqueductal gray or inferior colliculus as unconditioned stimulus are differentially regulated by 5-HT2A receptors in rats

Cited by 69 publications

References 56 publications

Apomorphine Enhances Conditioned Responses Induced by Aversive Stimulation of the Inferior Colliculus

Apomorphine Enhances Conditioned Responses Induced by Aversive Stimulation of the Inferior Colliculus

Lesion of the Ventral Periaqueductal Gray Reduces Conditioned Fear but Does Not Change Freezing Induced by Stimulation of the Dorsal Periaqueductal Gray

Serotonergic Modulation of Plasticity of the Auditory Cortex Elicited by Fear Conditioning

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