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Background This is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was hypothesized there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with noninvasive MRI. Methods The transgenic BBZDR/Wor rat, an animal model of T2MD, and age‐matched controls were studied for changes in brain structure using voxel‐based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting‐state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site‐specific data on over 168 different brain areas. Results There was an overall reduction in brain volume focused primarily on the somatosensory cortex, cerebellum, and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus. Conclusion The neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.

Social norms and legality surrounding the use of medical and recreational cannabis are changing rapidly. The prevalence of cannabis use in adolescence is increasing. The aim of this study was to assess any sex-based neurobiological effects of chronically inhaled, vaporised cannabis on adolescent female and male mice.Female and male mice were exposed daily to vaporised cannabis (10.3% Δ-9-tetrahydrocannabinol [THC] and 0.05% cannabidiol [CBD]) or placebo from postnatal day 23 to day 51. Following cessation of treatment, mice were examined for changes in brain structure and function using noninvasive multimodal magnetic resonance imaging (MRI). Data from voxel-based morphometry, diffusion weighted imaging and rest state functional connectivity were registered to and analysed with a 3D mouse atlas with 139 brain areas. Following imaging, mice were tested for their preference for a novel object.The effects were sexually dimorphic with females showing a unique distribution and inverse correlation between measures of fractional anisotropy and apparent diffusion coefficient localised to the forebrain and hindbrain. In contrast males displayed significant increased functional coupling with the thalamus, hypothalamus and brainstem reticular activating system as compared with controls. Cannabis males also presented with altered hippocampal coupling and deficits in cognitive function.Chronic exposure to inhaled vaporised cannabis had significant effects on brain structure and function in early adulthood corroborating much of the literature. Females presented with changes in grey matter microarchitecture, while males showed altered functional connectivity in hippocampal circuitry and deficits in object recognition.

The aim of this study was to assess the effects of two doses of Δ⁹-tetrahydrocannabinol (THC, cannabis’ main psychoactive agent) and vehicle on blood-oxygen-level dependent (BOLD) activity in drug-naive, awake rats, in an effort to obtain a THC-specific map of activation in clinically-relevant regions and systems. Intraperitoneal injections of low dose of THC resulted in an increased positive and negative BOLD signal compared to vehicle and high dose in areas rich in cannabinoid receptor 1, as well as throughout the pain and hippocampal neural systems. These results offer unique maps of activity, or “fingerprints”, associated with systemic THC administration, allowing for further comparisons with either additional doses or compounds, or between THC administration modalities (i.e. systemic vs ingested vs inhaled), which ultimately adds to the translatability assessment of THC-induced BOLD between animal and human studies. This article is protected by copyright. All rights reserved.

Clavulanic acid is a psychoactive compound with excellent blood-brain barrier permeability and safety profiles. Previous studies showed that clavulanic acid suppresses anxiety in rodents and in a primate model. In addition, clavulanic acid is thought to enhance sexual function in animal models via central nervous system (CNS) mechanisms. To further examine its potential as a CNS-modulating agent, we investigated the effects of clavulanic acid in neurotoxin-induced animal models that emulate neurodegenerative disease symptoms. Clavulanic acid was administered to rodents that were exposed to kainic acid or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Using histochemical staining of brain sections, we demonstrated that clavulanic acid protects hippocampal and dopaminergic neurons from toxin-induced acute death. We also observed that clavulanic acid improves motor function in MPTP-treated mice in a behavioral test. These data indicate that clavulanic acid may have neuroprotective effects and warrants further investigation of its therapeutic use in CNS disorders, such as Parkinson's and Alzheimer's disease. Drug Dev Res 71:351–357, 2010. © 2010 Wiley-Liss, Inc.

To compare and contrast the pattern and characteristics of the cerebral blood volume (CBV) response to ethanol (EtOH) in rats under awake and anesthetized conditions.Acute EtOH (0.75 g/kg) challenge-induced CBV changes were measured using a contrast-enhanced functional MRI CBV method in 15 male Sprague Dawley rats under three experimental conditions: 1.0% to 1.2% isoflurane (N = 5); 0.8% halothane (N = 5); and awake with no anesthetic (N = 5). Physiological parameters were collected from bench settings in nine rats from the above different conditions. Four parameters: 1) area under the curve (AUC%); 2) the maximum signal change (Max%); 3) EtOH absorption rate (alpha(2)); and 4) EtOH elimination rate (alpha(1)) were employed to compare EtOH-induced MRI signals between the awake and anesthetized groups.Both awake and anesthetized animals responded with an increase in CBV to EtOH challenge. However, the presence of anesthesia promoted a significant preferential flow to subcortical areas not seen in the awake condition.Unclear mechanisms of anesthesia add a layer of uncertainty to the already complex interpretation of EtOH's influence on neuronal activity, cellular metabolism, and hemodynamic coupling.

Functional magnetic resonance imaging (fMRI) is a unique window to the brain, enabling scientists to follow changes in brain activity in response to hormones, ageing, environment, drugs of abuse and other stimuli. There are two features that make fMRI unique when compared with other imaging modalities used in behavioural neuroscience. First, it can be entirely noninvasive: each animal can serve as its own control over the natural course of its life, vital for following neuroadaptation and other developmental processes critical to understanding behaviour. Second, fMRI has the spatial and temporal resolution to observe patterns of neuronal activity across the entire brain in less than a minute. Although fMRI does not have the cellular spatial resolution of immunostaining, nor the millisecond temporal resolution of electrophysiology, synchronised changes in neuronal activity across multiple brain areas seen with functional MRI can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviours. Thus, fMRI affords a systems approach to the study of the brain, complementing and building from other neurobiological techniques to understand how behaviour is organised across multiple brain regions. In this review, we present a general background to fMRI and the different imaging modalities that can be used in fMRI studies. Included are examples of the application of fMRI in behavioural neuroscience research, along with discussion of the advantages and disadvantages of this technology.

Summary: Purpose: Functional imaging of animal models makes it possible to map the functional neuroanatomy contributing to the genesis of seizures. Pentylenetetrazol (PTZ)-induced seizure in rats, a relevant model of human absence and of generalized tonic–clonic epilepsy, was used to stimulate seizure activity within 30 s of administration while collecting continuous, high-resolution, multislice images at subsecond intervals. Methods: Pilot studies were conducted to establish a quick and effective PTZ model for the imaging experiments. PTZ was then used to stimulate seizure activity in rats while collecting multislice functional MRI (fMRI) images from the entire forebrain at 4.7 Tesla. Ethosuximide (ESM) also was used to block seizure activity. Results: Within 2–4 s of PTZ administration, a rapid increase in blood oxygen level–dependent (BOLD) signal intensity was noted in the thalamus, especially the anterior thalamic nuclei. Activity in the anterior thalamus peaked ∼15 s before seizure onset and was more than twofold greater than that in all other thalamic areas. The retrosplenial cortex showed a twofold greater increase in activity as compared with other cortical areas, also peaking at ∼15 s. The dentate gyrus was twice as active as other hippocampal areas but peaked just before seizure onset. Treatment with ESM blocked seizures, decreasing PTZ-induced activation in most forebrain areas. The anterior thalamus and retrosplenial cortex were essentially blocked by pretreatment with ESM. Conclusions: The anterior thalamus, retrosplenial cortex, and dentate gyrus show the greatest increases in BOLD signal activity before seizure onset. Neurons in these areas may contribute to the neural network controlling the initiation of generalized tonic–clonic seizure.

Antipsychotic drugs regulate gene transcription in striatal neurons by blocking dopamine D2-like receptors. Little is known about the underlying changes in chromatin structure, including covalent modifications at histone N-terminal tails that are epigenetic regulators of gene expression. We show that treatment with D2-like antagonists rapidly induces the phosphorylation of histone H3 at serine 10 and the acetylation of H3-lysine 14 in bulk chromatin from striatum and in nuclei of striatal neurons. We find that, in vivo, D2-like antagonist-induced H3 phospho-acetylation is inhibited by the NMDA receptor antagonist MK-801 and by the protein kinase A (PKA) inhibitor Rp-adenosine 3c’,5c’-cyclic monophosphorothioate triethylammonium salt but increased by the PKA activator Sp-adenosine 3c’,5c’-cyclic monophosphorothioate triethylammonium salt. Furthermore, in dissociated striatal cultures which lack midbrain and cortical pre-synaptic inputs, H3 phospho-acetylation was induced by glutamate, l-type Ca2+ channel agonists and activators of cAMP-dependent PKA but inhibited by NMDA receptor antagonists or PKA antagonists. The dual modification, H3pS10-acK14, was enriched at genomic sites with active transcription and showed the kinetics of the early response. Together, these results suggest that histone modifications and chromatin structure in striatal neurons are dynamically regulated by dopaminergic and glutamatergic inputs converging on the cellular level. Blockade of D2-like receptors induces H3 phospho-acetylation, H3pS10-acK14, through cAMP-dependent PKA, and post-synaptic NMDA receptor signaling.

Summary: Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level–dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure.

A new approach to design uniplanar gradient coils for magnetic resonance imaging (MRI) is presented. The theoretical formulation involves a constraint cost function between the desired field in a particular region of interest in space and the current-carrying coil plane based on Biot-Savart's integral equation. An appropriate weight function in conjunction with linear approximation functions allows the transformation of the problem formulation into a linear matrix equation in which its iterative solution yields discrete current elements in terms of magnitude and direction within the prescribed coil plane. These current elements can be synthesized into an overall practical wire configuration by suitably adding individual wire loops. Numerical predictions and practical testing for a Gy gradient coil underscore the success of this approach in terms of achieving a highly linear field while maintaining low parasitic fields. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 20B: 17–29, 2004

During adolescence or adulthood, male hamster siblings were divided into control and experimental groups and exposed to periods of either mild or traumatic stress outside their individual nests. Mild stress is the simple exposure to a novel environment while the traumatic stressor is repeated daily subjugation by a dominant hamster. Over adolescence and adulthood, animals had free access to alcohol. The behavior and neuroendocrinology were assessed over these developmental periods in response to these environmental conditions. As adults, animals with a history of traumatic stress in adolescence showed inappropriate and excessive aggressive behavior. Their aggression was context dependent. In the presence of equal size hamsters, they showed little aggression; however, they were excessively aggressive toward smaller, younger animals. Testosterone levels and reproductive behavior were normal after adolescent subjugation; however, release of cortisol during agonistic encounters was suppressed. In comparison, hamsters exposed to chronic social subjugation as adults had low plasma testosterone, reduced reproductive behavior, and exaggerated cortisol release during agonistic encounters. Self-ingestion of alcohol during adolescence enhanced testosterone release around the peripubertal period but reduced plasma testosterone levels in adulthood. Exposure to alcohol as adolescents enhanced aggression in adulthood. These data demonstrate a pronounced difference in behavior and neuroendocrinology between adolescent and adult hamsters in their response to traumatic stress.

Prenatal exposure to nicotine has been associated with changes in behavioral indices in offspring. Flank marking, a scent-marking behavior in golden hamsters, appears to be controlled by arginine vasopressin (AVP) neurons in the hypothalamus. The present study examines the effects of prenatal exposure to nicotine on the vasopressinergic system associated with flank marking behavior.

Objectives: Current evidence suggests that mortality from acute organophosphate (OP) poisoning is partially mediated through central nervous system (CNS) respiratory center depression (CRD). However, the exact mechanism of OPinduced CRD is unknown. In these studies, the authors investigated the hypothesis that OP-induced CRD is the result of overstimulation of CNS respiratory centers. Methods: Wistar rats received prophylaxis with either normal saline (controls), atropine, the peripherally acting anticholinergics glycopyrrolate (GLYC), ipratropium bromide (IB), or the CNS respiratory center attenuator diazepam. To determine if a dual CNS/peripheral cholinergic mechanism is responsible for animal death, two additional groups received combination treatment with diazepam plus either IB or GLYC. All treatments were completed 5 minutes before OP with subcutaneous dichlorvos. Differences in 10minute and 24-hour mortality were assessed by the Fisher exact test. Results: Dichlorvos poisoning resulted in profound fasciculations without obvious seizure in all cohorts. In controls and animals treated with peripherally acting anticholinergics, fasciculations were followed by sedation and respiratory arrest (0% 10-minute survival in all cohorts). In contrast, pretreatment with either atropine or diazepam significantly improved 10-minute survival (100% and 44%, respectively). Although GLYC or IB afforded no protection when given alone, when delivered in conjunction with diazepam, the combination significantly improved survival (both groups 88% at 24 hours), suggesting a dual CNS/ pulmonary muscarinic mechanism of lethality. Conclusions: The central respiratory depressant diazepam paradoxically attenuates organophosphate-induced respiratory depression, and when combined with peripherally acting anticholinergic agents, reduces mortality in a rat model of severe acute OP poisoning. Key words: organophosphate; dichlorvos; poisoning; rat. ACADEMIC EMERGENCY MEDICINE 2003; 10:1303‐1306. Organophosphate (OP) poisoning produces significant morbidity and mortality throughout the industrialized and third worlds, with an estimated 3,000,000 exposures each year. 1 Additionally, weaponized OP or nerve agents threaten mass casualties despite the stockpiling of antidotes in the United States and abroad. 2 Given the potential for a mass poisoning complicated by a shortage of antidote, a complete understanding of the effects of these poisons might yield effective adjunctive therapies and prophylactic strategies that will protect individuals at high risk for lethal OP poisoning. 3,4

Summary: Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level–dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using γ-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike–wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents.

Changes in cortical activity during foot shock were assessed under conscious and propofol-anesthetized conditions using functional magnetic resonance imaging (fMRI). Increases in signal intensity were observed in the contralateral somatosensory cortex in response to electrical shock of the hindpaw under both conditions. These increases in cortical signal ranged from 6% to 26% while awake and from 1% to 6% under propofol anesthesia. In each of the six animals studied, the largest increase in blood oxygenation level-dependent (BOLD)-based signal intensity was observed during consciousness. In three of six animals, propofol anesthesia depressed signal intensity by as much as 10-fold, showing that the level of cortical activity during foot shock is dampened by anesthesia. These results indicate it would be advantageous to use fully conscious animals to maximize BOLD-based MRI signal in certain behavioral studies using MR spectrometers with modest field strengths (1.0-2.0 T).

These data suggest that shock stress during adolescence increases ETOH consumption and may contribute to an increase in aggression in early adulthood. Interestingly, shock stress without ETOH results in timid behavior in early adulthood. One might speculate that adolescent hamsters "self-medicate" to deal with continuous stress. However, because of the variability between experimental groups, it is necessary to replicate these studies with larger numbers of animals and expand the findings to include blood ETOH concentrations.

Golden hamsters start displaying flank marking behavior (a form of scent marking) around postnatal day 20 (P-20). Because the behavior is dependent upon the central activity of arginine vasopressin (AVP), the present study was conducted to correlate this activation with changes in the vasopressinergic system. A first set of experiments was performed to compare flank marking activity between P-18 and P-22. A second set of experiments was performed to compare the density of AVP receptors between the age periods and assess responsiveness to AVP microinjection. Finally, a third set of experiments incorporated immunocytochemistry, radioimmunoassay, in situ hybridization, and Northern blot analysis to determine the location and numbers of AVP immunoreactive neurons and the level of mRNA correlating with the developmental onset of flank marking behavior. Our results show that flank marking develops between P-18 and P-22. Male and female hamsters do not display odor-induced flank marking anytime before P-19. However, all animals show odor-induced flank marking by P-22. The onset of flank marking does not appear to be associated with any change in AVP receptor binding in the anterior hypothalamus. Indeed, flank marking can be triggered in hamsters on P-18 by the microinjection of AVP in the anterior hypothalamus. This would suggest that the postsynaptic mechanisms contributing to the transduction of the AVP signal and the motor control of flank marking are intact prior to the onset of odor-induced flank marking. In contrast, AVP levels in the hypothalamus and pituitary increase by two to threefold between P-18 and P-22, suggesting that changes in AVP synthesis and release from presynaptic sites may contribute to the onset of flank marking. Interestingly, there is no change in AVP mRNA between P-18 and P-22, which raises questions about posttranslational processing during this developmental period. These results suggest that heightened synthesis and release of AVP between P-18 and P-22 may contribute to the developmental onset of flank marking.

The present study was done to determine whether the vasopressinergic neurons in the hypothalamus controlling flank marking behavior are distinct from the magnocellular neurons comprising the hypothalamo-neurohypophysial system. Animals were either hypophysectomized or injected with a suicide transport lectin, volkensin, into the neurohypophysis. Both procedures resulted in a pronounced loss of vasopressin-immunoreactive perikarya throughout the hypothalamus concomitant with increases in water intake and urine output and decreases in circulating levels of vasopressin. The loss of the hypothalamo-neurohypophysial system was most pronounced in volkensin-treated animals that presented with frank diabetes insipidus and exceedingly low levels of plasma vasopressin. However, the vasopressinergic fibers and magnocellular neurons in and around the anterior hypothalamus implicated in the control of flank marking survived the volkensin treatment. Volkensin-treated animals exhibited levels of flank marking typical of untreated animals. These data suggest the presence of anatomically and functionally distinct populations of vasopressinergic magnocellular neurons in the hypothalamus of the golden hamster.

Site-, context- and dose-dependent actions of intrahypothalamic cortisol administration on the agonistic behaviors of adult male golden hamsters (n = 128 dyads) were examined. When cortisol-treated animals were tested in paired encounters with aggressive cholesterol-treated opponents, chronic (/= 24 h) cortisol treatment (1 mm implants) induced significant (P0.05) submission in three medial hypothalamic areas (anterior hypothalamic areamedial preoptic areaventromedial hypothalamus), but aggression in the paraventricular nucleus or third ventricle. In contrast, chronic cortisol treatment in the anterior hypothalamic area resulted in high levels of aggression during paired encounters with submissive opponents, and during territorial aggression tests with juvenile male intruders. Acute (/= 20 min) cortisol treatment in the anterior hypothalamic area (100 nl injections) induced significant submission after 10(-2) M, but significant aggression after 10(-6) M microinjections in paired encounters with aggressive vehicle-injected opponents. These findings suggest glucocorticoid-sensitive mechanisms within the anterior hypothalamus modulate aggressive responding during intrasexual social encounters.

Vasopressin-sensitive neurons in the region of the anterior hypothalamus are necessary for the mediation of flank marking behavior in the Golden hamster. The precise nature of the vasopressinergic innervation to the anterior hypothalamus is unknown. In this study we seek to examine the potential sources of this innervation by mapping and counting the vasopressin-immunoreactive neurons that contribute to the hypothalamo-neurohypophysial system, and those that do not. Vasopressin-immunoreactive neurons in the hypothalamus were visualized by immunocytochemistry. Sections were mapped with a computer-aided microscope system, and labeled neurons counted. Two-dimensional maps were stacked into a three-dimensional wireframe model which could be manipulated for further examination. The average number of vasopressin neurons was 3,135, with over 60% of all perikarya localized to the lateral supraoptic nucleus. In a double-labeling study, neurons contributing to the hypothalamo-neurohypophysial system were retrogradely labeled by the injection of horseradish peroxidase into the neurohypophysis. The enzyme reaction product was visualized by treatment with tetramethylbenzidine followed by nickel-conjugated diaminobenzidine. Sections were subsequently stained for vasopressin by immunocytochemistry. Single- and double-stained neurons from serial sections were mapped and counted. Wireframe and contoured three-dimensional representations were generated. The average number of neurons projecting to the neurohypophysis was 5,619. However, an average of 981 neurons was immunoreactive to vasopressin but devoid of horseradish peroxidase. The greatest number of these non-projecting perikarya were found in and around the anterior hypothalamus, localized primarily in the lateral and medial aspect of the supraoptic nuclei, the ventral area of the paraventricular nucleus, and the nucleus circularis. By comparing the number of non-projecting neurons found by double-staining to the total cell count of the entire vasopressin system, it was estimated that approximately 30% of all vasopressin neurons in and around the anterior hypothalamus did not project to the neurohypophysis. Based on the distribution and localization of the non-projecting perikarya, it is speculated that these neurons may provide neurotransmitter for vasopressin-dependent flank marking in the male Golden hamster.

It is well established that flank marking behavior in the Golden hamster is controlled by vasopressin-sensitive neurons localized to the anterior hypothalamus; however, the source(s) of vasopressinergic innervation to this area is unknown. Previous analysis by immunocytochemistry showed distinct populations of vasopressinergic magnocellular neurons localized to the supraoptic nucleus, paraventricular nucleus and the nucleus circularis that did not project to the neurohypophysis. In the present study, these same hypothalamic nuclei were lesioned by microinjection of kainic acid to determine which, if any, of these populations of vasopressin neurons are involved in the control of flank marking. Unilateral lesions in the areas of the nucleus circularis and supraoptic nucleus at the rostro-caudal plane of the anterior hypothalamus abolished odor-induced flank marking behavior. Lesions in the paraventricular nucleus at the level of the anterior hypothalamus did not consistently inhibit flank marking, while lesions of magnocellular neurons rostral or caudal to the anterior hypothalamus were ineffective. The microinjection of vasopressin into the anterior hypothalamus following lesion of the paraventricular and supraoptic nuclei stimulated flank marking, evidence that treatment with kainic acid did not damage the efferent component of this behavior. However, animals with lesions in the nucleus circularis did not respond to the microinjection of vasopressin; hence, it is uncertain whether lesions in this area disrupt vasopressinergic innervation to the anterior hypothalamus or simply destroy the motor neurons controlling flank marking. In summary, the data clearly demonstrate that vasopressin neurons localized primarily to the medial aspect of the supraoptic nucleus are necessary for sensory integration of odor-induced flank marking, and as such, may be one possible source of neurotransmitter controlling this behavior.

Golden hamsters with established dominant/subordinate relationships communicate their social status by rubbing pheromone-producing flank glands against objects in the environment. This behavior, called flank marking, is controlled by vasopressin-sensitive neurons localized to the anterior hypothalamus. Vasopressinergic magnocellular neurons in the nucleus circularis and medial aspect of the supraoptic nucleus are thought to be a source of neurotransmitter for the initiation of flank marking. The present study was undertaken to examine the extrahypothalamic control of flank marking. The anatomical and functional connections between the lateral septum and the vasopressin-containing nuclear groups in and around the anterior hypothalamus were examined by: (1) tracing afferent and efferent connections following microinjection of horseradish peroxidase and Phaseolus vulgaris-leucoagglutinin into the lateral septum, and (2) recording odor-induced flank marking prior to and following ibotenate lesions in the septum. The greatest number of perikarya retrogradely labeled with horseradish peroxidase were found lateral to the anterior hypothalamus and ventral to the fornix in the area of the lateral hypothalamus. The vasopressin-containing nuclear groups, e. g., paraventricular, supraoptic, suprachiasmatic nuclei, and the nucleus circularis, were devoid of labeled perikarya. Nerve terminals anterogradely labeled with Phaseolus vulgaris-leucoagglutinin were primarily localized to the anterior hypothalamus, in and around the nucleus circularis, and the medial aspect of the supraoptic nucleus. The lateral aspect of the supraoptic nucleus was devoid of nerve terminals as were the paraventricular and suprachiasmatic nuclei. The anatomical connections between the lateral septum and the hypothalamus appear to be necessary for the control of flank marking, since the microinjection of ibotenate into this limbic site significantly reduced odor-induced flank marking as compared to control microinjections of 0.9% NaCl.

Purpose: The development of non‐invasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. Magnetic Cationic Liposomes (MCL) that carry a cargo of anti‐cancer drugs and magnetic nanoparticles that will selectively target primary and metastatic cancertumorsdeliver drugs to them and visualize their effects through magnetic resonance imaging(MRI)single photon emission computed tomography(SPECT) and fluorescence spectroscopy. The aim of the present study is to evaluate MCL as a versatile theranostic nanoplatform for enhanced drug deliveryimaging and monitoring of cancer treatment. Materials and Method: Poly‐ethyleneglycol (PEG) coated cationic liposomes are loaded with superparamagnetic iron oxide nanoparticles (SPIONS) and tagged with the radioisotope Indium‐111. MCL was administered to SCID mouse with metastatic (B16‐F10) melanoma grown in the right flank. Pre‐injection and post‐injection MR and SPECT/CT images were used to assess response to magnetic targeting effects and tumor and organ distribution. Results:Tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2‐fold greater accumulation by magnetic targeting. SPECT/CT images showed the localization and distribution of MCL in the tumor.Conclusion: MR SPECT/CT and biodistribution analyses clearly show the efficacy of MCL as MRI contrast agents prove the use of magnetic guidance and demonstrate the potential of MCL as agents for imaging guidance and therapeutic delivery.

The present study examines the effect of the arginine vasopressin (AVP) receptor antagonist, d(CH2)5Tyr(Me)AVP, on intraspecific aggression between pairs of male Golden hamsters in a neutral territory. Subjects drawn from a group of 24 animals were paired once each with novel partners from the group under each of three experimental conditions: 1) both members of a pair were microinjected into the anterior hypothalamus with saline (S/S), 2) one member of a pair was microinjected with AVP-receptor antagonist and its partner with saline (A/S), and 3) both members of a pair were microinjected with AVP-receptor antagonist (A/A). There were significantly (P < .01) fewer attacks during encounters between pairs of hamsters in the A/A condition compared to pairs in the A/S condition. Similarly, pairs in the A/S condition attacked significantly (P < .025) less often than pairs of hamsters in the S/S condition. These results confirm our earlier work showing that AVP-receptor antagonist reduces intraspecific aggression. In addition, saline-treated hamsters initiated significantly (P < .001) fewer attacks toward antagonist treated hamsters than would have been predicted if their opponent was not drug treated. These latter results suggest that hamsters microinjected into the anterior hypothalamus with an AVP-receptor antagonist also elicit less aggression from conspecifics.