Intravenous loss of over-the-wire catheter guidewires in 13 horses.

BACKGROUND: Over-the-wire (OTW) catheter placement is performed frequently in horses. Intravascular loss of a guidewire has been anecdotally reported, but there is limited information regarding the treatment and outcome of horses that have experienced this complication of OTW catheter placement. OBJECTIVES: Describe the clinical and diagnostic features, treatment, and outcome of horses experiencing IV guidewire loss at the time of OTW catheter placement. ANIMALS: Thirteen horses. METHODS: Multicenter retrospective study to identify horses with IV guidewire loss. Horses of all ages were considered for inclusion. Horses were excluded from the study if complete medical records of signalment, indication, and outcome were not available. Intravenous guidewire loss was defined as the guidewire being lost IV at the time of OTW catheter placement. RESULTS: No horses in this study experienced adverse clinical signs associated with the loss of a guidewire. Eight horses had the guidewire removed and the guidewire was left in situ in 5 horses. None of the horses with the guidewire in situ had experienced long-term effects. CONCLUSIONS AND CLINICAL IMPORTANCE: Intravenous guidewire loss seems to have a good long-term prognosis even in horses in which removal of the guidewire was not possible. Thus, in horses where guidewire removal is not feasible, guidewires that remain in situ may have limited to no adverse effects.

Risk factors associated with an outbreak of equine coronavirus at a large farm in North Carolina.

Background: Equine coronavirus (ECoV) leads to outbreaks with variable morbidity and mortality. Few previous reports of risk factors for infection are available in the literature. Objectives: To describe unique clinical findings and risk factors for infection and development of clinical disease. Animals: 135 horses on a farm affected by ECoV outbreak. Methods: Retrospective cohort study. Data obtained included age, breed, gender, activity level, housing, and feed at the onset of the outbreak. Factors were evaluated for assessment of risk of infection using simple logistic regression or Fisher's exact test. Significance was set at p ≤ 0.05. Results and findings: Forty-three of 54 (79.6%) horses tested on the farm were positive on fecal PCR for ECoV, and 17 horses (12.6%) developed clinical signs consistent with ECoV. Out of 17 horses in which the presence or absence of signs of colic was noted, 6 of 17 (35.3%) showed signs of colic. Three of these horses had small colon impactions, 2 of which required surgical intervention. Significant risk factors for having positive PCR results included being primarily stalled (OR 167.1, 95% CI 26.4-1719), housing next to a positive horse (OR 7.5, 95% CI 3.1-19.0), being in work (OR 26.9, 95% CI 4.6-281.9), being fed rationed hay vs. ad libitum (OR 1,558, 95% CI 130.8-15,593), and being fed alfalfa hay (OR 1,558, 95% CI 130.8-15,593). Conclusions and clinical importance: This report describes risk factors for ECoV infection many of which were associated with intensive management of show horses. Clinicians should be aware that clinical signs vary and can include severe colic.

General anesthesia does not induce ultrasonographic changes in the pleura of healthy adult horses anesthetized for elective magnetic resonance imaging.

OBJECTIVE: To compare thoracic ultrasonographic findings in healthy horses before and after general anesthesia for elective MRI utilizing a recently developed ultrasonographic scoring system to aid clinicians in the early identification of pneumonia following anesthesia. ANIMALS: 13 adult horses > 3 years of age. PROCEDURES: Prior to anesthesia, horses underwent a thorough physical examination, CBC, thoracic radiography, and thoracic ultrasonography. Horses were then anesthetized for elective MRI, and thoracic ultrasonography was repeated within 3 hours after recovery. Thoracic ultrasonographic findings were scored utilizing a recently developed scoring system, and scores were compared before and after anesthesia. RESULTS: There was no significant difference identified in total thoracic ultrasonography score before and after anesthesia, and there was no correlation between thoracic ultrasonography score following anesthesia and the body weight of the horse, the time recumbent, and the dependent side. CLINICAL RELEVANCE: In healthy horses undergoing anesthesia for elective imaging, there was no significant change in thoracic ultrasonographic findings 3 hours after recovery from anesthesia. These data can aid clinicians in determining the clinical significance of ultrasonographic changes in the lung in the immediate postanesthetic period.

Comparison of thoracic ultrasonography and thoracic radiography between healthy adult horses and horses with bacterial pneumonia using a novel, objective ultrasonographic scoring system.

Background: Thoracic ultrasonography (TUS) is widely used in equine practice but comparison to radiography is limited in horses. Objectives: To validate a novel, objective scoring system for TUS in adult horses and to compare ultrasonographic and radiographic findings. Animals: 13 healthy horses and 9 with confirmed bacterial pneumonia. Methods: Prospective study in which TUS and radiography were performed on healthy horses and those with bacterial pneumonia confirmed by clinical signs and results of transtracheal wash analysis. Ultrasonography was scored utilizing a novel scoring system evaluating number of comet tail lesions, the presence or absence of pleural effusion and/or pulmonary consolidation in each intercostal space. Eighteen horses had thoracic radiographs taken that were scored by a board-certified radiologist utilizing a previously described system. Total scores were recorded and compared between control and diseased patients. Results/Findings: Ultrasonographic scores were significantly higher in the diseased group (median= 126) than in the control group (median = 20, p = 0.01). Receiver operating characteristics (ROC) analysis identified a sensitivity of 66.7% (95% CI 0.417-1) and specificity of 92.3% (95% CI 0.462-1) for the ability of ultrasonography to identify bacterial pneumonia utilizing a TUS score cutoff of 37. Conclusions and clinical importance: TUS had moderate sensitivity and high specificity for identification of bacterial pneumonia in adult horses. TUS appears to be an acceptable stand-alone imaging modality for diagnosis of bacterial pneumonia in horses when radiography is not practical.

Review: Investigating the aggregation of amyloid beta with surface plasmon resonance: Do different approaches yield different results?

Aggregation of amyloid beta into amyloid plaques in the brain is a hallmark characteristic of Alzheimer's disease. Therapeutics aimed at preventing or retarding amyloid formation often rely on detailed characterization of the underlying mechanism and kinetics of protein aggregation. Surface plasmon resonance (SPR) spectroscopy is a robust technique used to determine binding affinity and kinetics of biomolecular interactions. This approach has been used to characterize the mechanism of aggregation of amyloid beta but there are multiple pitfalls that need to be addressed when working with this and other amyloidogenic proteins. The choice of method for analyte preparation and ligand immobilization to a sensor chip can lead to different theoretical and practical implications in terms of the mathematical modelling of binding data, different mechanisms of binding and the presence of different interacting species. This review examines preparation methods for SPR characterisation of the aggregation of amyloid beta and their influence on the findings derived from such studies.

Comparison of Fluid Analysis and Cytologic Findings of Cerebrospinal Fluid Between Three Collection Sites in Adult Equids With Neurological Disease.

Cerebrospinal fluid (CSF) is routinely collected from three sites in the horse, the atlanto-occipital (AO), atlantoaxial (AA), and lumbosacral (LS) space. A comparison between fluid analysis parameters [total protein, total nucleated cell count (TNCC), red blood cell (RBC) count, and morphologic analysis] from samples obtained at each of the three sites has not previously been performed. A retrospective analysis was performed to evaluate the differences in fluid analysis of CSF between the AO, AA, and LS sites in equids presented to a referral service for evaluation of suspected neurological disease. A total of 113 equids aged ≥1 year that underwent CSF collection between 2008 and 2020 were included. Total nucleated cell count, RBC concentration, total protein (TP), and morphologic evaluation between CSF samples obtained from the three sites were compared. When comparing all samples, LS centesis was associated with higher RBC compared to other sites (p < 0.05); TP was lower in the AA group than in the LS group (p < 0.05). Within a subset of cytologically unremarkable samples, RBC concentration was highest in LS samples (p < 0.01); TP was higher in LS samples compared to AA samples (p < 0.05) and TNCC was higher (p < 0.01) in AA and LS groups compared to the AO. In cytologically abnormal samples, there were no significant differences between sites in any parameter. Abnormal cytology was correlated with non-survival (p = 0.0002). Non-survival was associated with higher TNCC (p < 0.01). The receiver operating characteristic (ROC) curve for TNCC had an area under the curve of 0.67 (95% CI, 0.55-0.79) and indicated that a cutoff value of 24 cells/µL maximized specificity (72%) and sensitivity (54%) to predict non-survival in all horses. Positive predictive value was 45%; negative predictive value was 78%. The concentration of RBC was higher in samples from the LS site. This has clinical implications due to the importance of comparative diagnostics and its potential impact on cytologic evaluation. There were minimal differences in multiple other parameters between sites, which are likely clinically insignificant.

Novel Amylin Analogues Reduce Amyloid-ß Cross-Seeding Aggregation and Neurotoxicity.

BACKGROUND: Type 2 diabetes related human islet amyloid polypeptide (hIAPP) plays a dual role in Alzheimer's disease (AD). hIAPP has neuroprotective effects in AD mouse models whereas, high hIAPP concentrations can promote co-aggregation with amyloid-ß (Aß) to promote neurodegeneration. In fact, both low and high plasma hIAPP concentration has been associated with AD. Therefore, non-aggregating hIAPP analogues have garnered interest as a treatment for AD. The aromatic amino acids F23 and I26 in hIAPP have been identified as the key residues involved in self-aggregation and Aß cross-seeding. OBJECTIVE: Three novel IAPP analogues with single and double alanine mutations (A1 = F23, A2 = I26, and A3 = F23 + I26) were assessed for their ability to aggregate, modulate Aß oligomer formation, and alter neurotoxicity. METHODS: A range of biophysical methods including Thioflavin-T, gel electrophoresis, photo-crosslinking, circular dichroism combined with cell viability assays were utilized to assess protein aggregation and toxicity. RESULTS: All IAPP analogues showed significantly less self-aggregation than hIAPP. Co-aggregated Aß42-A2 and A3 also showed reduced aggregation compared to Aß42-hIAPP mixtures. Self- and co-oligomerized A1, A2, and A3 exhibited random coil conformations with reduced beta sheet content compared to hIAPP and Aß42-hIAPP aggregates. A1 was toxic at high concentrations compared to A2 and A3. However, co-aggregated Aß42-A1, A2, or A3 showed reduced neurotoxicity compared to Aß42, hIAPP, and Aß42-hIAPP aggregates. CONCLUSION: These findings confirm that hIAPP analogues with non-aromatic residues at positions 23 and 26 have reduced self-aggregation and the ability to neutralize Aß42 toxicity. This warrants further characterization of their protective effects in pre-clinical AD models.

Design and Characterization of a Cell-Penetrating Peptide Derived from the SOX2 Transcription Factor.

SOX2 is an oncogenic transcription factor overexpressed in nearly half of the basal-like triple-negative breast cancers associated with very poor outcomes. Targeting and inhibiting SOX2 is clinically relevant as high SOX2 mRNA levels are positively correlated with decreased overall survival and progression-free survival in patients affected with breast cancer. Given its key role as a master regulator of cell proliferation, SOX2 represents an important scaffold for the engineering of dominant-negative synthetic DNA-binding domains (DBDs) that act by blocking or interfering with the oncogenic activity of the endogenous transcription factor in cancer cells. We have synthesized an interference peptide (iPep) encompassing a truncated 24 amino acid long C-terminus of SOX2 containing a potential SOX-specific nuclear localization sequence, and the determinants of the binding of SOX2 to the DNA and to its transcription factor binding partners. We found that the resulting peptide (SOX2-iPep) possessed intrinsic cell penetration and promising nuclear localization into breast cancer cells, and decreased cellular proliferation of SOX2 overexpressing cell lines. The novel SOX2-iPep was found to exhibit a random coil conformation predominantly in solution. Molecular dynamics simulations were used to characterize the interactions of both the SOX2 transcription factor and the SOX2-iPep with FGF4-enhancer DNA in the presence of the POU domain of the partner transcription factor OCT4. Predictions of the free energy of binding revealed that the iPep largely retained the binding affinity for DNA of parental SOX2. This work will enable the future engineering of novel dominant interference peptides to transport different therapeutic cargo molecules such as anti-cancer drugs into cells.

Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues.

Drug-reward cues trigger motivational circuitry, a response linked to drug-seeking in animals and in humans. Adverse life events have been reported to increase sensitivity to drug rewards and to bolster drug reward signaling. Therefore, we hypothesized that cocaine-dependent individuals with prior emotional, physical and sexual abuse might have a heightened mesolimbic brain response to cues for drug reward in a new brief-cue probe. Cocaine-dependent human individuals (N = 68) were stabilized in an inpatient setting and then completed an event-related blood-oxygen-level dependent functional magnetic resonance imaging task featuring 500-ms evocative (cocaine, sexual, aversive) and comparator (neutral) cues. Responses to three questions about emotional, physical and sexual abuse from the Addiction Severity Index were used to divide the patients into subgroups (history of Abuse [n = 40] versus No Abuse [n = 28]). When subjects were grouped by the historical presence or absence of emotional, physical or sexual abuse, the Abuse group showed a heightened midbrain, thalamic, caudate, and caudal orbitofrontal cortex response to cocaine cues; a similar result was found in other evocative cues, as well. These findings are the first reported for a 500-ms cocaine-cue probe, and they highlight the ability of very brief evocative cues to activate the brain's motivational circuitry. Although all participants had severe cocaine use disorders, individuals reporting prior abuse had a heightened mesolimbic response to evocative cues. To our knowledge, this is the first study in humans linking a history of abuse to a brain vulnerability (heightened mesolimbic response to drug cues) previously shown to contribute to drug-seeking.

Oxytocin reverses amphetamine-induced deficits in social bonding: evidence for an interaction with nucleus accumbens dopamine.

Drug addiction has devastating consequences on social behaviors and can lead to the impairment of social bonding. Accumulating evidence indicates that alterations in oxytocin (OT) and dopamine (DA) neurotransmission within brain reward circuitry may be involved. We investigated this possibility, as well as the therapeutic potential of OT for drug-induced social deficits, using the prairie vole (Microtus ochrogaster)-a socially monogamous rodent that forms enduring pair bonds between adult mates. We demonstrate that repeated exposure to the commonly abused psychostimulant amphetamine (AMPH) inhibits the formation of partner preferences (an index of pair bonding) in female prairie voles. AMPH exposure also altered OT and DA neurotransmission in regions that mediate partner preference formation: it decreased OT and DA D2 receptor immunoreactivity in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc), respectively, and increased NAcc DA levels. Administration of OT directly into the mPFC of AMPH-exposed voles restored partner preferences, and altered NAcc DA levels, and this effect was dependent on OT receptor activation. Together, these data suggest that repeated AMPH exposure impairs pair bonding through an OT-mediated mechanism, and that OT and DA systems within brain reward circuitry may interact to mediate the complex relationship between drug abuse and social bonding. Further, these results provide empirical support for the idea that the central OT system may represent an important target for the treatment of social deficits in addiction.

Nipping cue reactivity in the bud: baclofen prevents limbic activation elicited by subliminal drug cues.

Relapse is a widely recognized and difficult to treat feature of the addictions. Substantial evidence implicates cue-triggered activation of the mesolimbic dopamine system as an important contributing factor. Even drug cues presented outside of conscious awareness (i.e., subliminally) produce robust activation within this circuitry, indicating the sensitivity and vulnerability of the brain to potentially problematic reward signals. Because pharmacological agents that prevent these early cue-induced responses could play an important role in relapse prevention, we examined whether baclofen-a GABAB receptor agonist that reduces mesolimbic dopamine release and conditioned drug responses in laboratory animals-could inhibit mesolimbic activation elicited by subliminal cocaine cues in cocaine-dependent individuals. Twenty cocaine-dependent participants were randomized to receive baclofen (60 mg/d; 20 mg t.i.d.) or placebo. Event-related BOLD fMRI and a backward-masking paradigm were used to examine the effects of baclofen on subliminal cocaine (vs neutral) cues. Sexual and aversive cues were included to examine specificity. We observed that baclofen-treated participants displayed significantly less activation in response to subliminal cocaine (vs neutral) cues, but not sexual or aversive (vs neutral) cues, than placebo-treated participants in a large interconnected bilateral cluster spanning the ventral striatum, ventral pallidum, amygdala, midbrain, and orbitofrontal cortex (voxel threshold p < 0.005; cluster corrected at p < 0.05). These results suggest that baclofen may inhibit the earliest type of drug cue-induced motivational processing-that which occurs outside of awareness-before it evolves into a less manageable state.

Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals.

RATIONALE: Addiction theories posit that drug-related cues maintain and contribute to drug use and relapse. Indeed, our recent study in cocaine-dependent patients demonstrated that subliminally presented cocaine-related stimuli activate reward neurocircuitry without being consciously perceived. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent drug-seeking behaviors. OBJECTIVES: Using an equivalent paradigm, we tested whether cannabis cues activate reward neurocircuitry in treatment-seeking, cannabis-dependent individuals and whether activation was associated with relevant behavioral anchors: baseline cannabis craving (drug-seeking behavior) and duration of use (degree of conditioning). METHODS: Twenty treatment-seeking, cannabis-dependent individuals (12 males) underwent event-related blood oxygen level-dependent functional magnetic resonance imaging during exposure to 33-ms cannabis, sexual, and aversive cues presented in a backward-masking paradigm. Drug use history and cannabis craving were assessed prior to imaging. RESULTS: Participants showed increased activity to backward-masked cannabis cues in regions supporting reward detection and interoception, including the left anterior insula, left ventral striatum/amygdala, and right ventral striatum. Cannabis cue-related activity in the bilateral insula and perigenual anterior cingulate cortex was positively associated with baseline cannabis craving, and cannabis cue-related activity in the medial orbitofrontal cortex was positively correlated with years of cannabis use. Neural responses to backward-masked sexual cues were similar to those observed during cannabis cue exposure, while activation to aversive cues was observed only in the left anterior insula and perigenual anterior cingulate cortex. CONCLUSIONS: These data highlight the sensitivity of the brain to subliminal reward signals and support hypotheses promoting a common pathway of appetitive motivation.

The impact of sex on brain responses to smoking cues: a perfusion fMRI study.

BACKGROUND: Anecdotal and clinical theories purport that females are more responsive to smoking cues, yet few objective, neurophysiological examinations of these theories have been conducted. The current study examines the impact of sex on brain responses to smoking cues. METHODS: Fifty-one (31 males) cigarette-dependent sated smokers underwent pseudo-continuous arterial spin-labeled perfusion functional magnetic resonance imaging during exposure to visual smoking cues and non-smoking cues. Brain responses to smoking cues relative to non-smoking cues were examined within males and females separately and then compared between males and females. Cigarettes smoked per day was included in analyses as a covariate. RESULTS: Both males and females showed increased responses to smoking cues compared to non-smoking cues with males exhibiting increased medial orbitofrontal cortex and ventral striatum/ventral pallidum responses, and females showing increased medial orbitofrontal cortex responses. Direct comparisons between male and female brain responses revealed that males showed greater bilateral hippocampal/amygdala activation to smoking cues relative to non-smoking cues. CONCLUSIONS: Males and females exhibit similar responses to smoking cues relative to non-smoking cues in a priori reward-related regions; however, direct comparisons between sexes indicate that smoking cues evoke greater bilateral hippocampal/amygdalar activation among males. Given the current literature on sex differences in smoking cue neural activity is sparse and incomplete, these results contribute to our knowledge of the neurobiological underpinnings of drug cue reactivity.

Social bonding decreases the rewarding properties of amphetamine through a dopamine D1 receptor-mediated mechanism.

Although the protective effects of social bonds on drug use/abuse have been well documented, we know little about the underlying neural mechanisms. Using the prairie vole (Microtus ochrogaster)--a socially monogamous rodent that forms long-term pair bonds after mating--we demonstrate that amphetamine (AMPH) conditioning induced a conditioned place preference (CPP) in sexually naive (SN), but not pair-bonded (PB), males. Although AMPH treatment induced a similar magnitude of dopamine release in the nucleus accumbens (NAcc) of SN and PB males, it had differential effects on NAcc D1 receptor (D1R) binding. Specifically, AMPH treatment increased D1R binding in SN, but decreased D1R binding in PB males. NAcc D1R, but not D2 receptor, antagonism blocked AMPH-induced CPP in SN males and NAcc D1R activation before AMPH conditioning enabled AMPH-induced CPP in PB males. Together, our data demonstrate that pair-bonding experience decreases the rewarding properties of AMPH through a D1R-mediated mechanism.

Amphetamine alters behavior and mesocorticolimbic dopamine receptor expression in the monogamous female prairie vole.

We have recently established the socially monogamous prairie vole (Microtus ochrogaster) as an animal model with which to investigate the involvement of mesocorticolimbic dopamine (DA) in the amphetamine (AMPH)-induced impairment of social behavior. As the majority of our work, to date, has focused on males, and sex differences are commonly reported in the behavioral and neurobiological responses to AMPH, the current study was designed to examine the behavioral and neurobiological effects of AMPH treatment in female prairie voles. We used a conditioned place preference (CPP) paradigm to determine a dose-response curve for the behavioral effects of AMPH in female prairie voles, and found that conditioning with low to intermediate (0.2 and 1.0 mg/kg), but not very low (0.1 mg/kg), doses of AMPH induced a CPP. We also found that exposure to a behaviorally relevant dose of AMPH (1.0 mg/kg) induced an increase in DA concentration in the nucleus accumbens (NAcc) and caudate putamen but not the medial prefrontal cortex or ventral tegmental area (VTA). Finally, repeated AMPH exposure (1.0 mg/kg once per day for 3 consecutive days; an injection paradigm that has been recently shown to alter DA receptor expression and impair social bonding in male prairie voles) increased D1, but not D2, receptor mRNA in the NAcc, and decreased D2 receptor mRNA and D2-like receptor binding in the VTA. Together, these data indicate that AMPH alters mesocorticolimbic DA neurotransmission in a region- and receptor-specific manner, which, in turn, could have profound consequences on social behavior in female prairie voles.

The role of mesocorticolimbic dopamine in regulating interactions between drugs of abuse and social behavior.

The use of addictive drugs can have profound short- and long-term consequences on social behaviors. Similarly, social experiences and the presence or absence of social attachments during early development and throughout life can greatly influence drug intake and the susceptibility to drug abuse. The following review details this reciprocal interaction, focusing on common drugs of abuse (e.g., psychostimulants, opiates, alcohol and nicotine) and social behaviors (e.g., maternal, sexual, play, aggressive and bonding behaviors). The neural mechanisms underlying this interaction are discussed, with a particular emphasis on the involvement of the mesocorticolimbic dopamine system.

The neurobiology of pair bonding: insights from a socially monogamous rodent.

The formation of enduring relationships between adult mates (i.e., pair bonds) is an integral aspect of human social behavior and has been implicated in both physical and psychological health. However, due to the inherent complexity of these bonds and the relative rarity with which they are formed in other mammalian species, we know surprisingly little about their underlying neurobiology. Over the past few decades, the prairie vole (Microtus ochrogaster) has emerged as an animal model of pair bonding. Research in this socially monogamous rodent has provided valuable insight into the neurobiological mechanisms that regulate pair bonding behaviors. Here, we review these studies and discuss the neural regulation of three behaviors inherent to pair bonding: the formation of partner preferences, the subsequent development of selective aggression toward unfamiliar conspecifics, and the bi-parental care of young. We focus on the role of vasopressin, oxytocin, and dopamine in the regulation of these behaviors, but also discuss the involvement of other neuropeptides, neurotransmitters, and hormones. These studies may not only contribute to the understanding of pair bonding in our own species, but may also offer insight into the underlying causes of social deficits noted in several mental health disorders.

Agonistic encounters and brain activation in dominant and subordinate male greater long-tailed hamsters.

During an agonistic encounter test, dominant male greater long-tailed hamsters (Tscheskia triton) initiated attacks sooner and displayed higher levels of aggression and flank marking behavior than their subordinate counterparts. Accordingly, subordinate males exhibited more defensive behavior than dominant ones. Specific patterns of neuronal activation, measured by Fos-immunoreactive staining (Fos-ir), were found in the hamster brain following agonistic interactions. Increased Fos-ir was observed in the bed nucleus of the stria terminalis (BST), ventromedial hypothalamus (VMH), and medial (MeA) and anterior cortical (ACo) nuclei of the amygdala (AMYG) in both dominant and subordinate males. In contrast, dominant males had significantly higher Fos-ir densities in the medial preoptic area (MPOA) than subordinate males, whereas subordinate males expressed higher densities of Fos-ir in the anterior hypothalamus (AH) and central nucleus of the amygdala (CeA). Additionally, Fos-ir levels in the MPOA were significantly correlated with aggression and Fos-ir levels in the AH and CeA were correlated with defensive behavior. Together, our data indicate distinct patterns of neuronal activation associated with agonistic encounters in a behavior-specific manner in male greater long-tailed hamsters.

Nucleus accumbens dopamine mediates amphetamine-induced impairment of social bonding in a monogamous rodent species.

The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating, a behavior in which central dopamine (DA) has been implicated. Here, we used male prairie voles to examine the effects of drug exposure on pair bonding and related neural circuitry. In our first experiment, amphetamine (AMPH) motivated behavior was examined using a conditioned place preference (CPP) paradigm and was shown to be mediated by activation of D1-like DA receptors. Next, we examined the effects of repeated AMPH exposure on pair bonding. Intact and saline pretreated control males displayed mating-induced partner preferences, whereas males pretreated with AMPH at the doses effective to induce CPP failed to show mating-induced partner preferences. Such AMPH treatment also enhanced D1, but not D2, DA receptor expression in the nucleus accumbens (NAcc). Furthermore, pharmacological blockade of D1-like DA receptors in the NAcc rescued mating-induced partner preferences in AMPH-treated males. Together, our data indicate that repeated AMPH exposure may narrow the behavioral repertoire of male prairie voles via a DA receptor-specific mechanism in the NAcc, resulting in the impairment of pair bond formation.

Post-weaning social isolation alters anxiety-related behavior and neurochemical gene expression in the brain of male prairie voles.

Stressful social experiences early in life, such as maternal separation and social isolation, have enduring effects on the development of the brain and behavior. In the present study in socially monogamous male prairie voles (Microtus ochrogaster), we found that following 6 weeks of social isolation after weaning males spent more time in the closed arms and less time in the open arms during an elevated plus maze (EPM) test, moved more frequently from central to peripheral squares in an open field test, and diminished their preferences for the empty chamber during a two-chamber affiliation test, compared to control males that were housed with siblings. This increased behavioral anxiety in socially isolated males was also associated with enhanced mRNA expression for vasopressin (AVP), oxytocin (OT), corticotrophin releasing factor (CRF), and tyrosine hydroxylase (TH) in the paraventricular nucleus of the hypothalamus (PVN). Together, these data illustrate the importance of the post-weaning social environment on anxiety-related behavior and suggest a potential role of neurochemical systems in the PVN in the regulation of this behavior.