'ARVs are a constant reminder of lost freedom, whereas for others, they are liberating': understanding the treatment narrative among people living with HIV (PLHIV) in Malawi and Zimbabwe-a qualitative study.

OBJECTIVE: The aim of the research was to understand what drives and motivates young women living with HIV in their treatment journeys, as well as their key influencers. The findings will assist in appreciating their obstacles to treatment and constructing the most effective ways to convey fresh messages to them. These insights will contribute to the messaging developed for a campaign across sub-Saharan Africa, primarily Malawi and Zimbabwe. DESIGN: This was a qualitative study conducted in order to build an understanding of unknown parts of the HIV treatment journey through in-depth interviews. A hybrid approach was used to conduct thematic analysis. SETTING AND PARTICIPANTS: Study participants were HIV-positive women, their influencers (eg, parents/partners/siblings/aunts and uncles/religious leaders, etc) and healthcare providers from a range of regions in Zimbabwe and Malawi. RESULTS: A total of 26 young people living with HIV (PLHIV), 29 healthcare providers and 24 influencers such as maternal figures in the community were interviewed. Two main broad insights were drawn, that is, key needs and wider contextual factors. The key needs of young PLHIV to stay on treatment were empathy, support and emotional connection with antiretroviral therapy (ART), while the wider contextual factors impacting their treatment journeys were structural challenges and cultural reference points. Fear of shame and humiliation can also be significant barriers to disclosure and treatment. The fear predisposes the PLHIV to the need for empathy, support and connection with ART. Mental health and anxiety appear to be comorbid with HIV. Some PLHIV have a small and limited support network leading to very few people living openly with HIV. There is no 'one-size-fits-all' approach, and maximising campaign reach will likely need a multifaceted approach. CONCLUSION: Currently, the relationship between nurses and PLHIV can appear to be transactional. Through learning about the community (including PLHIV), there are more chances of communicating in a way that resonates.

Understanding Oral PrEP Interest, Uptake, Persistence, and Experience of Use Among Heterosexual Men in Johannesburg, South Africa: An Exploratory Pilot Study.

South Africa's PrEP programming has primarily focused on men who have sex with men and other key populations through dedicated clinical and outreach services. However, data shows that the pool of men vulnerable to contracting HIV extends beyond this group, including men who have sex only with women and who do not identify as gay. The aim of this pilot study was to assess acceptability of PrEP among this subset of men who are at risk of HIV acquisition in South Africa and to describe the demographic and behavioral characteristics of male PrEP users as well as their experience of PrEP use. We employed a mixed-methods study design consisting of in-depth interviews and quantitative analysis of routine clinic data collected between September 2021 and February 2022 from 10 private health facilities. Men who enrolled in the study and initiated PrEP had low consistent condom use and nearly three quarters reported more than one sexual partner in the past three months. Despite minimal follow-up support, PrEP persistence was relatively high and similar to other populations. 57% of men returned for their 1-month visit, 40% returned for their 4-month visit, and 16% returned for their 7-month visit. The greatest barriers to ongoing use were the need to take a daily pill and low perceived HIV risk. To improve uptake and continuation, programs should increase awareness of PrEP, leverage trusted sources to build credibility, make access more convenient, and accommodate flexible use through event-driven PrEP.

RESUMEN: La programación de la PrEP en Sudáfrica se ha centrado principalmente en los hombres que tienen sexo con hombres a través de servicios clínicos y de servicio de alcance comunitario específicos. Sin embargo, los datos muestran que el grupo de hombres vulnerables a contraer el VIH se extiende más allá de este grupo, e incluye a hombres que sólo tienen relaciones sexuales con mujeres y que no se identifican como homosexuales. El objetivo de este estudio piloto fue evaluar la aceptabilidad de la PrEP en este subgrupo de hombres en riesgo de contraer el VIH en Sudáfrica y describir las características demográficas y de comportamiento de los usuarios masculinos de la PrEP, así como su experiencia con el uso de la PrEP. Se empleó un diseño de estudio de métodos mixtos que consistió en entrevistas a profundidad y análisis cuantitativos de datos clínicos rutinarios recolectados entre septiembre de 2021 y febrero de 2022, en 10 centros sanitarios privados. Los hombres que se inscribieron en el estudio e iniciaron la PrEP tenían un bajo uso consistente de condón y casi tres cuartas partes declararon haber tenido más de una pareja sexual en los últimos tres meses. A pesar de tener un apoyo de seguimiento mínimo, la continuidad de la PrEP fue relativamente alta y similar a la de otras poblaciones. El 57% de los hombres volvieron a su visita de 1 mes, el 40% volvieron a su visita de 4 meses y el 16% volvieron a su visita de 7 meses. Las mayores barreras para el uso continuo fueron la necesidad de tomar una pastilla diaria y la baja percepción del riesgo de VIH. Para mejorar la aceptación y la continuidad, los programas deben aumentar la conciencia sobre la PrEP, aprovechar las fuentes de confianza para aumentar la credibilidad, hacer que el acceso sea más cómodo y permitir un uso flexible mediante la PrEP a demanda.

Uptake and Short-Term Retention in HIV Treatment Among Men in South Africa: The Coach Mpilo Pilot Project.

INTRODUCTION: Gender disparities persist across the HIV care continuum in sub-Saharan Africa. Men are tested, linked, and retained at lower rates than women. Men experience more treatment interruptions, resulting in higher rates of virological failure and increased mortality. Peer support is an approach to improving men's engagement and retention in HIV treatment. We assessed uptake and early retention in HIV care among men in the 'Coach Mpilo' peer support pilot project in South Africa. METHODS: We conducted a pilot project from March 2020 to September 2020 in 3 districts: Ehlanzeni and Gert Sibande (Mpumalanga) and Ugu (KwaZulu-Natal). Men living with HIV were invited to receive one-on-one coaching from a peer supporter who was stable on treatment. We analyzed participants' self-reported data on demographics, uptake, and retention in HIV treatment. We described baseline characteristics using summary statistics and reported uptake and early retention proportions overall and by testing history (newly and previously diagnosed). RESULTS: Among 4,182 men living with HIV, most were previously diagnosed (n=2,461, 64%) and uptake was high (92%, n=3,848). Short-term retention was 80% (n=1,979) among men previously diagnosed and 88% (n=1,213) among newly diagnosed. In September 2020, 95% (n=3,653/3,848) of all participants reported being active on HIV treatment, including those retained consistently and those who had interrupted and returned to care. Among participants experiencing treatment interruption after enrolling, the majority (82%, n=464) returned to treatment, largely within 2 months. CONCLUSIONS: Improving linkage to and retention in HIV treatment among men is essential for their health and for treatment as prevention. This pilot project provided preliminary evidence that a peer-led support model was acceptable, retained a high proportion of men in the early stages of ART, and supported men returning to care after treatment interruption. These promising results require further investigation to assess impact, scalability, and cost-effectiveness.

Targeting interventions for HIV testing and treatment uptake: An attitudinal and behavioural segmentation of men aged 20-34 in KwaZulu-Natal and Mpumalanga, South Africa.

Despite recent improvements, men still have worse HIV outcomes than women in South Africa. This study describes how young men form distinct behavioural and attitudinal subgroups, and is intended to inform the design of targeted interventions to encourage HIV testing and initiation on antiretroviral therapy. Data were collected using a cross-sectional survey with questions on men's attitudes, beliefs and behaviours around HIV/AIDS. A total of 2,019 men were randomly sampled from eight district municipalities in KwaZulu-Natal and Mpumalanga provinces between October 2018 and January 2019. Men were eligible to participate if they were aged 20-34, Black African, had an education level below university graduation, were aware of HIV and were willing to disclose whether they had tested for HIV. Each participant responded to a questionnaire asking about their demographic characteristics, reported sexual behaviour, engagement with HIV testing and treatment services, alcohol consumption, HIV knowledge, attitudes to gender equity and reported level of depressive symptoms. Data were analysed using canonical correlation, hierarchical clustering and factor analysis techniques to produce five groups of men. The results were synthesised using Human Centred Design principles to suggests areas for potential intervention for each segment. The results showed that men vary based on their attitudes to gender and masculinity, use of alcohol, testing and treatment behaviour, HIV-related fears and preferences for testing modalities. Segment 1 (21%) avoids the topic of HIV, perhaps fearful of the impact on his life. Segment 2 (23%) is well connected to his community and has social concerns about HIV. Segment 3 (15%) struggles with more distal determinants of HIV acquisition such as unemployment and poor mental health. Segment 4 (25%) has concerns about the lifestyle changes that would be required if he were HIV positive. Segment 5 (16%) has a strong traditional mindset and is fearful of the ramifications of HIV in his community. The results will be used to design targeted interventions to increase HIV testing and treatment rates among young men in South Africa. Further research is required to understand the impact of interventions designed in this way.

Strengthening measurement and performance of HIV prevention programmes.

Indicators for the measurement of programmes for the primary prevention of HIV are less aligned than indicators for HIV treatment, which results in a high burden of data collection, often without a clear vision for its use. As new evidence becomes available, the opportunity arises to critically evaluate the way countries and global bodies monitor HIV prevention programmes by incorporating emerging data on the strength of the evidence linking various factors with HIV acquisition, and by working to streamline indicators across stakeholders to reduce burdens on health-care systems. Programmes are also using new approaches, such as targeting specific sexual networks that might require non-traditional approaches to measurement. Technological advances can support these new directions and provide opportunities to use real-time analytics and new data sources to more effectively understand and adapt HIV prevention programmes to reflect population movement, risks, and an evolving epidemic.

Global implementation of PrEP for HIV prevention: setting expectations for impact.

INTRODUCTION: Questions remain whether HIV pre-exposure prophylaxis (PrEP) can be translated into a successful public health intervention, leading to a decrease in population-level HIV incidence. We use examples from HIV treatment and contraceptives to discuss expectations for PrEP uptake, adherence, and persistence and their combined impact on the epidemic. DISCUSSION: Targets for PrEP uptake must be based on the local HIV epidemic and will depend on appropriate estimates of the key populations at risk for HIV. However, there is evidence that targets, once established, can successfully be met and that uptake may increase with awareness. Messaging around adherence should include that daily adherence is the goal (except for those MSM for whom event-driven dosing is a good fit), but perfect adherence should not be a barrier. Ideally, clients persist on PrEP for as long as they are at risk for HIV. While PrEP will be most effective when coverage is focused on high-risk populations, normalizing rather than stigmatizing PrEP will be highly beneficial. CONCLUSIONS: While many challenges to PrEP implementation exist, we focused on the three key steps of uptake, adherence and persistence as measurable processes that can lead to improved coverage and decreased HIV incidence.

Implementation experiences and insights from the scale-up of an HIV assisted partner notification intervention in Central Asia.

INTRODUCTION: WHO recommends assisted partner notification (APN) for people living with HIV (PLHIV). These services have not been widely scaled in Central Asia. We describe the results from an APN intervention implemented within a programme focused on PLHIV and people who inject drugs in Kazakhstan, the Kyrgyz Republic and Tajikistan. METHODS: Routine data from index cases and their partners were analysed from equal-length periods before and after APN launch. Prior to APN index cases could recruit partners using passive referral, and under APN, had their choice of passive referral or APN (provider, contract or dual-referral). We compared the demographic characteristics of index cases and their sexual/injecting partners from the pre-APN and APN periods, described the number/proportion of HIV cases found (positivity rate) and evaluated predictors of HIV infection among partners using logistic regression. RESULTS: Under APN 2676 PLHIV served as index cases and recruited 3735 partners for testing, compared to 4418 index cases and 2240 partners during the pre-APN period. A total of 322 (8.6%) partners were rapid test positive during APN versus 161 (7.2%, p = 0.048) before APN. Women represented 38% of APN index cases (vs. 42% pre-APN), 52% of partners tested (vs. 50% pre-APN) and 56% of all PLHIV identified (vs. 63% pre-APN). Compared to the pre-APN period, the number of partners tested per index case recruited increased (0.5 to 1.4, p < 0.001) and the number of index cases needed to find one HIV-positive partner decreased significantly (27.4 to 8.3, p < 0.001) under APN. CONCLUSIONS: APN was feasibly integrated within a people who inject drugs and PLHIV-focused HIV programme, and was acceptable to high-risk populations in Central Asia. Under APN, large numbers of sexual and injecting partners of PLHIV - including women and non-marital partners - were tested while maintaining high positivity rates. Relative to the pre-APN period, APN approximately tripled the number of partners recruited per index case and reduced the number of index cases needed to find a positive partner by >3 times.

Adolescent Sexual and Reproductive Health Services and Implications for the Provision of Voluntary Medical Male Circumcision: Results of a Systematic Literature Review.

BACKGROUND: Voluntary medical male circumcision (VMMC) is a critical HIV prevention tool. Since 2007, sub-Saharan African countries with the highest prevalence of HIV have been mobilizing resources to make VMMC available. While implementers initially targeted adult men, demand has been highest for boys under age 18. It is important to understand how male adolescents can best be served by quality VMMC services. METHODS AND FINDINGS: A systematic literature review was performed to synthesize the evidence on best practices in adolescent health service delivery specific to males in sub-Saharan Africa. PubMed, Scopus, and JSTOR databases were searched for literature published between January 1990 and March 2014. The review revealed a general absence of health services addressing the specific needs of male adolescents, resulting in knowledge gaps that could diminish the benefits of VMMC programming for this population. Articles focused specifically on VMMC contained little information on the adolescent subgroup. The review revealed barriers to and gaps in sexual and reproductive health and VMMC service provision to adolescents, including structural factors, imposed feelings of shame, endorsement of traditional gender roles, negative interactions with providers, violations of privacy, fear of pain associated with the VMMC procedure, and a desire for elements of traditional non-medical circumcision methods to be integrated into medical procedures. Factors linked to effective adolescent-focused services included the engagement of parents and the community, an adolescent-friendly service environment, and VMMC counseling messages sufficiently understood by young males. CONCLUSIONS: VMMC presents an opportune time for early involvement of male adolescents in HIV prevention and sexual and reproductive health programming. However, more research is needed to determine how to align VMMC services with the unique needs of this population.

Integrating prevention interventions for people living with HIV into care and treatment programs: a systematic review of the evidence.

INTRODUCTION: This review assesses the impact of prevention interventions for people living with HIV on HIV-related mortality, morbidity, retention in care, quality of life, and prevention of ongoing HIV transmission in resource-limited settings (RLSs). METHODS: We conducted a systematic review of studies reporting the results of prevention interventions for people living with HIV in RLS published between January 2000 and August 2014. Standardized methods of searching and data abstraction were used. RESULTS: Ninety-two studies met the eligibility criteria: 24 articles related to adherence counseling and support, 13 on risk reduction education and condom provision, 19 on partner HIV testing and counseling, 14 on provision of family planning services, and 22 on assessment and treatment of other sexually transmitted infections. Findings indicate good evidence that adherence counseling and sexually transmitted infection treatment can have a high impact on morbidity, whereas risk reduction education, partner HIV testing and counseling, and family planning counseling can prevent transmission of HIV. More limited evidence was found to support the impact of these interventions on retention in care and quality of life. Most studies did not report cost information, making it difficult to draw conclusions about the cost-effectiveness of these interventions. CONCLUSIONS: This evidence suggests that these prevention interventions, if brought to sufficient scale and coverage, can help support and optimize the impact of core treatment and prevention interventions in RLS. Further operational research with more rigorous study designs, and ideally with biomarkers and costing information, is needed to determine the best model for providing these interventions in RLS.

Prevention of sexually transmitted HIV infections through the President's Emergency Plan for AIDS Relief: a history of achievements and lessons learned.

HIV prevention in the President's Emergency Plan for AIDS Relief (PEPFAR) began when both data on HIV prevalence and the toolbox of interventions for prevention of sexual transmission were relatively limited. PEPFAR's early focus was on scaling-up information, education, and communication programs that included messaging on abstinence for youth and faithfulness primarily through nongovernmental organizations, including faith-based organizations. Additional activities included condom promotion, distribution, and social marketing. In epidemics concentrated within key populations, PEPFAR's prevention efforts focused on a minimum package of services including outreach, information, education, and communication programs, STI treatment (where appropriate), and condom promotion and distribution. As more epidemiological data became available and with experience gleaned in these early efforts, the need for tailored and flexible approaches became evident. The next iteration of prevention efforts still emphasized behavioral interventions, but incorporated a sharper focus on key epidemic drivers, especially multiple partners; a data-driven emphasis on high transmission areas and populations, including prevention with people living with HIV; and a more strategic and coordinated approach at the national level. Recently, the paradigm for prevention efforts has shifted yet again. Evidence that biomedical interventions such as male circumcision, treatment for prevention of vertical and horizontal transmission, and treatment itself could lead to declines in incidence has refocused PEPFAR's prevention portfolio. New guidance on sexually transmitted HIV focuses on combination prevention, emphasizing biomedical, behavioral and structural approaches. Landmark speeches by the President and the Secretary of State and new ambitious targets for PEPFAR point toward a new goal: an AIDS-free generation.

HIV prevention transformed: the new prevention research agenda.

We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.

Social isolation reduces mammary development, tumor incidence, and expression of epigenetic regulators in wild-type and p53-heterozygotic mice.

Chronic stress is associated with more rapid tumor progression, and recent evidence suggests that stress may contribute to social and ethnic disparities in the incidence and mortality of breast cancer. We evaluated the p53(+/-) FVB/N mouse as a model to investigate effects of chronic social stress on mammary gland development, gene expression, and tumorigenesis. We individually housed (IH) wild-type and p53(+/-) female FVB/N mice, starting at weaning. At 14 weeks of age, both wild-type and p53(+/-) IH mice showed strikingly reduced mammary development compared with group-housed (GH) controls, with IH mice having significantly fewer preterminal end buds. This morphologic difference was not reflected in levels of mammary transcripts for estrogen receptor-alpha or progestin receptor. However, IH increased levels of mRNA for the kisspeptin receptor in the medial preoptic area of the hypothalamus, associated with reduced duration of estrous cycles. Furthermore, IH altered mammary transcripts of genes associated with DNA methylation; transcripts for methyl-binding protein 2 and DNA methyltransferase 3b (DNMT3b), but not DNMT1 and DNMT3a, were reduced in IH compared with GH females. Interestingly, the glands of p53(+/-) females showed reduced expression of all these mediators compared with wild-type females. However, contrary to our initial hypothesis, IH did not increase mammary tumorigenesis. Rather, p53(+/-) GH females developed significantly more mammary tumors than IH mice. Together, these data suggest that social isolation initiated at puberty might confound studies of tumorigenesis by altering mammary development in mouse models.

Maternal aggression: new insights from Egr-1.

Lactating mice display fierce aggression towards novel, male mice. This study compares neuronal activity in the brains of aggression-tested (T) and -untested (U) mice using early growth response factor 1 (Egr-1; also known as Krox 24, NGFI-A, Zif268, Tis8, and ZENK) as a measure of neuronal activity. Animals were sampled 90 min after either a sham or real 7-min test with a male intruder, after which their brains were examined for immunoreactivity to Egr-1 (Egr-IR). Significant increases in Egr-IR in T mice were identified in 11 of 40 brain regions, including paraventricular nucleus of the hypothalamus; anterior and lateral hypothalamus (both posterior portion); ventromedial hypothalamus; lateral periaqueductal gray; and medial, central, and basolateral amygdala. Posterodorsal (MePD) and posteroventral medial amygdala were examined for the first time in association with maternal aggression. MePD, a region associated with both sexual and aggressive behaviors in rats, hamsters, and mice, showed increased Egr-IR in association with testing. Taken together, the results from this study provide new insights into the neural circuits regulating maternal behaviors.

Gene array profiling of large hypothalamic CNS regions in lactating and randomly cycling virgin mice.

A dramatic example of neuronal and physiological plasticity in adult mammals occurs during the transition from a non-maternal to a maternal, lactating state. In this study, we compared gene expression within a large continuous region of the CNS involved in maternal behaviors (hypothalamus, preoptic regions, and nucleus accumbens) between lactating (L) (postpartum Day 7) and randomly cycling virgin (V) outbred mice. Using high-density oligonucleotide arrays representing 11,904 genes, two statistical algorithms were used to identify significant differences in gene expression: robust multiarray (P < 0.001) (n = 92 genes) and significance analysis of microarrays using a 10% false discover rate (n = 114 genes). 27 common genes were identified as significant using both techniques. A subset of genes (n = 5) were selected and examined by real-time PCR. Our findings were consistent with previous published work. For example, neuropeptide Y (NPY) and proenkephalin were elevated in L mice, whereas POMC was decreased. Increased levels of NPY Y2 receptor and polo-like kinase and decreased levels of endothelin receptor type b in L mice are examples of novel gene expression changes not previously identified. Expression differences occurred in broad classes. Together, our findings provide possible new material on gene expression changes that may support maternal behaviors. The advantages and drawbacks of sampling large CNS regions using arrays are discussed.

Differential fos activation in virgin and lactating mice in response to an intruder.

Lactating (L) mice display fierce aggression towards novel, male mice, while virgin (V) mice do not. This study compares patterns of brain activation in V and L mice in response to a novel intruder using immunohistochemical detection of Fos (Fos-IR). Animals were sampled 120 min after either a sham or real 10 min test with a male intruder. L mice were aggressive towards intruders, but V mice were not. In general, Fos-IR for both groups increased with exposure to an intruder, with L mice showing higher increases in Fos-IR than V mice. In only medial preoptic nucleus and ventral portion of bed nucleus of stria terminalis (BNST) was Fos-IR significantly increased in both groups with testing. In V mice, testing resulted in Fos-IR increases in an additional 10 regions examined that did not reach significance in L mice, including lateral septum, lateral and medial preoptic areas, and anterior hypothalamus. Fos-IR also increased with testing in nine regions unique to L mice, including the mitral and granular layers of accessory olfactory bulb, regions of the amygdala, dorsal BNST, and caudal portions of the hypothalamic attack area. These increases in Fos-IR with testing suggest alterations in the circuitry governing response to pheromonal cues and imply some commonalities between the circuitries governing maternal aggression and intermale aggression. These results support the hypothesis that pregnancy and lactation induce substantial changes in brain circuitry and function; changes that enable maternal defense of offspring by altering the neural response to an intruder male.

Elevated stress sensitivity in corticotropin-releasing factor receptor 2 deficient mice decreases maternal, but not intermale aggression.

Maternal aggression is a form of aggression towards intruders by lactating females that is critical for defense of offspring. During lactation, fear and anxiety are reduced, the CNS is less responsive to the anxiogenic neuropeptide, corticotropin-releasing factor (CRF), and central injections of CRF inhibit maternal aggression. Together, these previous findings suggest that decreased CRF neurotransmission during lactation supports normal maternal aggression expression. Recent work indicates that mice deficient in CRF receptor 2 (CRFR2) display increased anxiety-like behaviors, have a hypersensitive stress response, and overproduce CRF. In this study, we examined both maternal and intermale aggression in wild-type (WT) and CRFR2-deficient mice. CRFR2-mutant mice exhibited significant deficits in maternal aggression on postpartum Day 4 relative to WT mice in terms of percentage displaying aggression, mean number of attacks, and mean time in aggressive encounters. However, time sniffing male intruder, pup retrieval, number of pups, and performance on the elevated plus maze were similar between genotypes. In contrast, intermale aggression did not differ between genotype in any measure on any of three consecutive test days. For neither form of aggression did sites of attacks on the intruder differ between genotype. Taken together, the results suggest that differences in stress sensitivity and the overproduction of CRF of the knockout (KO) mice specifically affects maternal, but not intermale aggression.

Predatory aggression, but not maternal or intermale aggression, is associated with high voluntary wheel-running behavior in mice.

Predatory (towards crickets), intermale, and maternal aggression were examined in four replicate lines of mice that had been selectively bred for high wheel-running (S) and in four random-bred control lines (C). In generation 18, individual differences in both predatory and intermale aggression were significantly consistent across four trial days, but predatory and intermale aggression were uncorrelated both at the individual level and among the eight line means. Latencies to attack crickets were significantly lower in S lines as a group. Intermale aggression, however, did not differ between S and C lines. S lines were significantly smaller in body mass, but did not differ in either testes mass or plasma testosterone. In generations 28 and 30, respectively, S and C lines did not differ in either maternal or intermale aggression. However, significant differences among the individual lines were found for maternal aggression, and one S line exhibited an extremely high mean time of aggression (>120 sec for a 5-min test). Maternal and intermale aggression were not correlated among the eight line means or at the level of individual variation. Overall, our results suggest: (1) predatory aggression and voluntary wheel-running are positively related at the genetic level; (2) predatory and intermale aggression are unrelated at a genetic level; and (3) maternal and intermale aggression are not tightly related at the genetic level. Possible relationships between predatory aggression, dopamine, and wheel-running behavior are discussed.