Effects of microinjections of apomorphine and haloperidol into the inferior colliculus on the latent inhibition of the conditioned emotional response

Electrical or chemical stimulation of the inferior colliculus (IC) induces fear-like behaviors. More recently, consistent evidence has shown that electrical stimulation of the central nucleus of the IC supports Pavlovian conditioning and latent inhibition (Li). LI is characterized by retardation in conditioning and also by an impaired ability to ignore irrelevant stimuli, after a non-reinforced pre-exposure to the conditioned stimulus. LI has been proposed as a behavioral model of cognitive abnormalities seen in schizophrenia. The aim of the present study was to determine whether dopaminergic mechanisms in the IC are involved in LI of the conditioned emotional response (CER). To induce LI, a group of rats was pre-exposed (PE) to six tones in two sessions, while rats that were not pre-exposed (NPE) had two sessions without tone presentations. The conditioning consisted of two tone presentations to the animal, followed immediately by a foot shock. PE and NPE rats received IC microinjections of physiological saline, the dopaminergic agonist apomorphine (9.0 mu g/0.5 mu L/side), or the dopaminergic antagonist haloperidol (0.5 mu g/0.5 mu L/side) before both pre-exposure and conditioning. During the test, the PE rats that received saline or haloperidol had a lower suppression of the licking response compared to NPE rats that received vehicle or haloperidol, indicating that latent inhibition was induced. There was no significant difference in the suppression ratio in rats that received apomorphine injections into the IC, indicating reduced latent inhibition. These results suggest that dopamine-mediated mechanisms of the IC are involved in the development of LI. (C) 2008 Elsevier Inc. All rights reserved.

Gabaergic mechanisms of hypothalamic nuclei in the expression of conditioned fear

The amygdala, the dorsal periaqueductal gray (dPAG), and the media] hypothalamus have long been recognized to be a neural system responsible for the generation and elaboration of unconditioned fear in the brain. It is also well known that this neural substrate is under a tonic inhibitory control exerted by GABA mechanisms. However, whereas there is a growing body of evidence to suggest that the amygdala and dPAG are also able to integrate conditioned fear, it is still unclear, however, how the distinct hypothalamic nuclei participate in fear conditioning. In this work we aimed to examine the extent to which the gabaergic mechanisms of this brain region are involved in conditioned fear using the fear-potentiated startle (FPS). Muscimol, a GABA-A receptor agonist, and semicarbazide, an inhibitor of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD), were used as an enhancer and inhibitor of the GABA mechanisms, respectively. Muscimol and semicarbazide were injected into the anterior hypothalamus (AHN). the dorsomedial part of the ventromedial nucleus (VMHDM), the dorsomedial (DMH) or the dorsal premammillary (PMD) nuclei of male Wistar rats before test sessions of the fear conditioning paradigm. The injections into the DMH and PMD did not produce any significant effects on FPS. On the other hand, muscimol injections into the AHN and VMHDM caused significant reduction in FPS. These results indicate that injections of muscimol and semicarbazide into the DMH and PMD fail to change the FPS, whereas the enhancement of the GABA transmission in the AHN and VMHDM produces a reduction of the conditioned fear responses. On the other hand, the inhibition of this transmission led to an increase of this conditioned response in the AHN. Thus, whereas DMH and PMD are known to be part of the caudal-most region of the medial hypothalamic defensive system, which integrates unconditioned fear, systems mediating conditioned fear select the AHN and VMHDM nuclei that belong to the rostral-most portion of the hypothalamic defense area. Thus, distinct subsets of neurons in the hypothalamus could mediate different aspects of the defensive responses. (C) 2008 Elsevier Inc. All rights reserved.

Regulation of conditioned and unconditioned fear in rats by 5-HT1A receptors in the dorsal periaqueductal gray

Studies on the involvement of 5-HT1-mediated mechanisms in the dorsal periaqueductal gray (dPAG) of animals with past stressful experiences have not been conducted so far. We investigated the role of 5-HT1 receptors in the dPAG of rats previously submitted to contextual fear conditioning. Defensive behaviors induced by activation of the dPAG were assessed by measuring the lowest electric current applied to this structure (threshold) able to produce freezing and escape responses during testing sessions of contextual fear conditioning, in which animals were placed in a context previously paired to footshocks. The 5-HT1A function of the dPAG was evaluated by local injections of 8-OH-DPAT (4 and 8 nmol/0.2 mu L) and WAY-100635 (10 nmol/0.2 mu L), selective agonist and antagonist of 5-HT1A receptors, respectively. In accordance with previous studies, 8-OH-DPAT increased aversive thresholds (antiaversive effects) but injections of WAY 100635 into the dPAG did not produce significant effects on the aversive thresholds in naive rats. However, the aversive thresholds of animals exhibiting contextual fear remained unchanged with both treatments. Moreover, 8-OH-DPAT and WAY 100635 did not change the dPAG post-stimulation freezing. The present results suggest that the stressful experience of being fear conditioned has an effect on the role of the 5-HT1A receptors in mediating unconditioned fear. Also, the reduction in the regulation of the defensive behaviors by 5-HT1A-mediated mechanisms in the dPAG of these animals may underlie the stress precipitated psychopathology associated with the neural substrates of aversion of the dPAG. (c) 2007 Elsevier Inc. All rights reserved.

Conditioned fear is modulated by D(2) receptor pathway connecting the ventral tegmental area and basolateral amygdala

Excitation of the mesocorticolimbic pathway, originating from dopaminergic neurons in the ventral tegmental area (VTA), may be important for the development of exaggerated fear responding. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. The functional role of the dopaminergic pathway connecting the VIA to the basolateral amygdala (BLA) in fear and anxiety has received little attention. In vivo microdialysis was performed to measure dopamine levels in the BLA of Wistar rats that received the dopamine D(2) agonist quinpirole (1 mu g/0.2 mu l) into the VTA and were subjected to a fear conditioning test using a light as the conditioned stimulus (CS). The effects of intra-BLA injections of the D(1) antagonist SCH 23390 (1 and 2 mu g/0.2 mu l) and D(2) antagonist sulpiride (1 and 2 mu g/0.2 mu l) on fear-potentiated startle (FPS) to a light-CS were also assessed. Locomotor performance was evaluated by use of open-field and rotarod tests. Freezing and increased dopamine levels in the BLA in response to the CS were both inhibited by intra-VTA quinpirole. Whereas intra-BLA SCH 23390 did not affect FPS, intra-BLA sulpiride (2 mu g) inhibited FPS. Sulpiride`s ability to decrease FPS cannot be attributed to nonspecific effects because this drug did not affect motor performance. These findings indicate that the dopamine D(2) receptor pathway connecting the ventral tegmental area and the basolateral amygdala modulates fear and anxiety and may be a novel pharmacological target for the treatment of anxiety. (C) 2010 Elsevier Inc. All rights reserved.

Serotonergic mechanisms of the median raphe nucleus-dorsal hippocampus in conditioned fear: Output circuit involves the prefrontal cortex and amygdala

Independent studies have shown that the median raphe nucleus (MRN) and dorsal hippocampus (DH) are involved in the expression of contextual conditioned fear (CFC). However, studies that examine the integrated involvement of serotonergic mechanisms of the MRN-DH are lacking. To address this issue, a CFC paradigm was used to test whether the serotonergic projections from the MRN to DH can influence CFC. Serotoninergic drugs were infused either into the MRN or DH prior to testing sessions in which freezing and startle responses were measured in the same context where 6 h previously rats received footshocks. A reduction of serotonin (5-HT) transmission in the MRN by local infusions of the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) decreased freezing in response to the context but did not reduce fear-potentiated startle. This pattern of results is consistent with the hypothesis that MRN serotonergic mechanisms selectively modulate the freezing response to the aversive context. As for the DH, a decrease in postsynaptic 5-HT receptor activity at projection areas has been proposed to be the main consequence of 5-HT(1A) receptor activation in the MIRN. Intra-DH injections of 8-OH-DPAT inhibited both the freezing and fear-potentiated startle response to the context. To reconcile these findings, an inhibitory mechanism may exist between the incoming 5-HT pathway from the MRN to DH and the neurons of the DH output to other structures. The DH-amygdala or medial prefrontal cortex projections could well be this output circuit modulating the expression of CFC as revealed by measurements of Fos immunoreactivity in these areas. (C) 2009 Elsevier B.V. All rights reserved.

Overshadowing in conditioned taste aversion or in conditioned emotional response after neonatal ventral hippocampal lesions in rats

The neonatal hippocampus lesion thought to model schizophrenia should show the same modifications in behavioural tests as other models, especially pharmacological models. namely decreased latent inhibition, blocking and overshadowing. The present study is set out to evaluate overshadowing in order to complement our previous studies, which had tested latent inhibition. ""Overshadowing"" refers to the decreased conditioning that occurs when the to-be-conditioned stimulus is combined with another stimulus at the conditioning stage. We used the same two Pavlovian conditioning paradigms as in our previous works, namely conditioned taste aversion (CTA) and conditioned emotional response (CER). A sweet taste overshadowed a salty conditioned stimulus, and a tone overshadowed a flashing light. Totally different stimuli were used to counter possible sensory biases. The protocols were validated with two groups of Sprague Dawley rats. The same two protocols were then applied to a cohort of rats whose ventral hippocampus had been destroyed when they were 7 days old. Only rats with extended ventral hippocampus lesions were included. The overall effect of Pavlovian conditioning was attenuated, significantly so in the conditioned emotional response paradigm, but overshadowing appeared not to be modified in either the conditioned emotional response or the conditioned taste aversion paradigm. (C) 2008 Elsevier B.V. All rights reserved.

2-perfect directed m-cycle systems can be equationally defined for m=3,4, and 5 only

It is shown that quasigroups constructed using the standard construction from 2-perfect directed m-cycle systems are precisely the finite members of a variety if and only if m=3, 4 or 5.

A family of perfect hashing methods

Minimal perfect hash functions are used for memory efficient storage and fast retrieval of items from static sets. We present an infinite family of efficient and practical algorithms for generating order preserving minimal perfect hash functions. We show that almost all members of the family construct space and time optimal order preserving minimal perfect hash functions, and we identify the one with minimum constants. Members of the family generate a hash function in two steps. First a special kind of function into an r-graph is computed probabilistically. Then this function is refined deterministically to a minimal perfect hash function. We give strong theoretical evidence that the first step uses linear random time. The second step runs in linear deterministic time. The family not only has theoretical importance, but also offers the fastest known method for generating perfect hash functions.

Lambda-fold 3-perfect 9-cycle systems

The spectrum for the decomposition of lambda K-v into 3-perfect 9-cycles is found for all lambda > 1. (The case lambda = 1 was dealt with in an earlier paper by the authors and Lindner.) The necessary conditions for the existence of a suitable decomposition turn out to be sufficient.

Strongly 2-perfect cycle systems and their quasigroups

A recent result of Bryant and Lindner shows that the quasigroups arising from 2-perfect m-cycle systems form a variety only when m = 3, 5 and 7. Here we investigate the situation in the case where the distance two cycles are required to be in the original system.

Conditioned inhibition of autonomic Pavlovian conditioning in humans

The present study aimed to demonstrate conditioned inhibition of Pavlovian conditioning of autonomic responses in humans. Subjects (N = 21) were presented initially with four geometric shapes (A, B, C and D). An electric shock served as the unconditioned stimulus (US) during acquisition. Conditional stimuli lasted for 8 s and US onset coincided with CS offset. Subjects were trained with A-US, C-US, and AC-US pairings and AB alone and B alone presentations. The subsequent summation test consisted of C-US pairings and CB alone and CD alone presentations. Conditioning was evident in self-reported US expectancy and first and second interval electrodermal responses. Evidence for conditioned inhibition during the summation test was found in US expectancy and second interval electrodermal responses. (C) 1997 Elsevier Science B.V.