Effects of an early experience of reward through maternal contact or its denial on the dopaminergic system of the rat brain.

The mesolimbic/mesocortical dopaminergic pathway plays a pivotal role in the reward system. During the neonatal period the mother is the main source of rewarding stimuli. We have developed an experimental model in which rat pups learn a T-maze during the neonatal period (postnatal day (PND) 10-13) using contact with the mother as the reward. One group of animals is allowed contact with the mother (receipt of expected reward, RER) while the other was denied (denial of expected reward, DER). We determined the effects of these two early experiences in the prefrontal cortex (PFC) and the nucleus accumbens (nAc), the levels of dopamine (DA) and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] by high-performance liquid chromatography and those of D1 and D2 receptors by autoradiographic in vitro binding both on PND 13 and in adulthood. On PND13, 2h after the end of training, the RER experience resulted in higher DA, HVA and D1 receptor levels in the nAc, while the DER in lower DA and its metabolites (DOPAC and HVA) in the PFC. These results could be related to the reward the RER pups received through the contact with their mother. The RER and DER early experience had long-term sex-dependent effects: The RER-induced activation of the dopaminergic system in the nAc was also evident in adult female rats. In contrast, adult DER males, similar to PND13 animals, had reduced dopamine in the PFC. Our results document that early experiences, a key determinant of adult brain function, affect the dopaminergic system which is disturbed in many psychiatric diseases.

Effects of interaction of an early experience of reward through maternal contact or its denial with social stress during adolescence on the serotonergic system and the stress responsiveness of adult female rats.

Experiences during critical periods, such as the neonatal and adolescence, play a critical role in determining adult stress-coping behavior. Based on the aforementioned we developed an experimental protocol, which included a neonatal experience and a social stress during adolescence. The serotonergic system is known as an important modulator of coping ability and, in general, emotional balance in both normal and pathological states, such as depression and anxiety, for which females are more vulnerable. Thus in the present work we used female rats and determined 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and 5-hydroxytryptamine receptor type 1A (5-HT(1A)) receptor levels in the prefrontal cortex (PFC) and the amygdala (AMY). During postnatal days 10-13 (PND 10-13) rat pups were exposed to a T-maze, one arm of which lead to the mother. One group of animals was allowed contact with the mother (rewarded-receiving expected reward (RER)), whereas the other was denied the expected reward (DER). High performance liquid chromatography (HPLC) analysis revealed that in both the PFC and in AMY, adult RER animals had higher basal 5-HT levels. Furthermore, in the AMY of this group of animals, higher levels of 5-HT(1A) receptors were detected by Western blot analysis. In adulthood rats were exposed to the Forced Swimming Test/Stress (FST/S). RER animals not exposed to the adolescent stress exhibited longer immobility time during both the first and second day of FST. Corticosterone levels following the FST fell faster in the DER animals. Adolescent stress affected the responses to the adult FSS only in the DER animals, which had decreased 5-HT in the AMY and increased immobility time on both days of the FST, compared with the DER, not stressed in adolescence. The phenotype of the DER animals is in line with the "match-mismatch" hypothesis, which states that if two events during critical periods of life "match" in being mildly stressful, their interaction can be adaptive.

Reward or its denial during the neonatal period affects adult spatial memory and hippocampal phosphorylated cAMP response element-binding protein levels of both the neonatal and adult rat.

Early life experiences, particularly mother-infant interactions, have been shown to influence adult coping and learning abilities via gene-environment interactions. We have developed a paradigm, in which mother contact is used as either a positive or a negative reinforcer in a T-maze, during postnatal days 10-13. In both neonates receiving (RER) or denied (DER) the expected reward, exposure to the memory test in the absence of the mother resulted in a remarkable increase in the number of pCREB immunopositive cells, when compared to their corresponding levels 2 h after the completion of the training process, but also to the levels of naïve animals. In the CA3 area, the pattern of pCREB immunoreactivity, when evaluated 2 h after the completion of the training on postnatal day 13 seemed to distinguish between the two different neonatal experiences in the T-maze, with the DER pups showing higher levels of pCREB immunopositive cells than the RER. Exposure to the Morris Water Maze (MWM) during adulthood revealed a memory advantage of the DER animals compared to the RER and the animals not exposed to the neonatal experience. Relevantly, in the DER animals an increased number of pCREB immunopositive cells was observed in the CA3 area even 24 h after the end of MWM training. When also measured after exposure to the probe trial, the number of pCREB immunopositive cells was again higher in the DER compared to the RER animals. In conclusion, we show that a learning experience involving discrepancy during the particularly plastic neonatal period is able to induce long-term effects, which result in enhanced adult hippocampal dependent spatial memory. Furthermore, our data document a role of plasticity molecules like pCREB in mediating hippocampal dependent learning and detection of novelty not only in adulthood, but also more importantly in the neonatal period of the rat.

Orbital cavernous hemangiomas: ultrasound and magnetic resonance imaging evaluation.

Cavernous hemangioma is the most common intraorbital lesion in adults. The aim of our study was to evaluate the magnetic resonance imaging (MRI) and ultrasound (US) characteristics of cavernous hemangioma and their role in the differential diagnosis of orbital tumors. Eight patients with orbital cavernous hemangiomas, five women and three men with a mean age of 48 years were examined in a period of six years. All patients underwent MRI examination and four patients were also evaluated by US. In all cases MRI depicted a well-defined intraconal tumor. The lesions were homogeneous, isointense to muscle on T1-weighted sequence and hyperintense to muscle on T2-weighted sequence in six patients. In one patient the mass was isointense on T1WI with heterogeneous signal intensity on T2WI and in one patient the lesion had heterogeneous signal intensity on both T1- and T2-weighted sequences. After intravenous contrast medium administration, the tumors showed initial inhomogeneous enhancement with progressive accumulation of contrast material on delayed images in seven patients and initial homogeneous enhancement in one patient. On ultrasonography, the orbital masses appeared slightly hyperechoic, heterogeneous with small areas of slow blood flow. The analysis of imaging characteristics of a well-defined intraconal lesion in an adult patient with painless progressive proptosis can be highly suggestive of the diagnosis of cavernous hemangioma.

Imaging findings of cavernous sinus hemangiomas. A report of two cases.

Extra-axial cavernous sinus hemangiomas are rare and account for less than 1% of parasellar tumors. These lesions have characteristic radiological features but the differential diagnosis from parasellar meningiomas and schwannomas can be difficult. Preoperative diagnosis is important due to the risk of severe intraoperative bleeding and the complex neurovascular structures of the cavernous sinus. We describe two cases of cavernous sinus hemangiomas and review the imaging findings of these lesions.

Effect of neonatal handling on adult rat spatial learning and memory following acute stress.

Brief neonatal handling permanently alters hypothalamic-pituitary-adrenal axis function resulting in increased ability to cope with stress. Since stress is known to affect cognitive abilities, in the present study we investigated the effect of brief (15 min) handling on learning and memory in the Morris water maze, following exposure to an acute restraint stress either before training or recall. Exposure of non-handled rats to the acute stress prior to training resulted in quicker learning of the task, than in the absence of the stressor. When acute stress preceded acquisition, male handled rats showed an overall better learning performance, and both sexes of handled animals were less impaired in the subsequent memory trial, compared to the respective non-handled. In addition, the number of neurons immunoreactive for GR was higher in all areas of Ammon's horn of the handled rats during the recall. In contrast, the number of neurons immunoreactive for MR was higher in the CA1 and CA2 areas of the non-handled males. When the acute restraint stress was applied prior to the memory test, neonatal handling was not effective in preventing mnemonic impairment, as all animal groups showed a similar deficit in recall. In this case, no difference between handled and non-handled rats was observed in the number of GR positive neurons in the CA2 and CA3 hippocampal areas during the memory test. These results indicate that early experience interacts with sex and acute stress exposure in adulthood to affect performance in the water maze. Hippocampal corticosterone receptors may play a role in determining the final outcome.

Treacher-collins syndrome and associated abnormalities. A case report.

Treacher-Collins syndrome or mandibulofacial dysostosis is an autosomal dominant disorder of craniofacial development. In this familial syndrome there is an arrest in the development of the facial bones, manifested by a depression of the malar bones, an antimonogoloid slant of the palpebral fissures, mandibular hypoplasia with retrognathia, coloboma of the lower eyelids and deformities of the ear structures derived from the branchial arches. Frequently, there is external auditory canal atresia and deformity of the pinnae. Other uncommon anomalies include congenital heart defects and cryptorchidism. This study describes a rare case of Treacher-Collins syndrome associated with congenital cardiopathy and megacolon, with a review of the literature.

Pneumosinus Dilatans Syndrome of the Sphenoid Sinus. A CT Evaluation.

This study discusses the CT findings of pneumosinus dilatans of the sphenoid sinus, highlighting the clinically important CT characteristics. The CT findings of 26 patients with overpneumatization of the sphenoid sinus are presented in correlation with the clinical findings. Twenty-two patients had overpneumatization beyond the boundaries of the body of the sphenoid bone with or without bone remodelling but only two patients reported headaches. Thinning of the bone structures was also present in three patients but only one patient reported headaches. Overpneumatization of the sphenoid sinus with thinning of bunywalls reduced the width of the superior orbital fissure in one patient resulting in a gradual decrease of visual acuity. CT is an accurate method for the evaluation of overpneumatization of the sphenoid sinus due to its high sensitivity in depicting evidence of bone erosion using a bone window as imaging settings.