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The Patient Rejection Scale in an Israeli sample: correlations with relapse and physician's assessment.

The Patient Rejection Scale (PRS), which was developed to assess the feelings of rejection that relatives experience toward mental patients, was administered to a sample of 50 family members living with schizophrenic outpatients in Jerusalem, Israel. PRS response distribution was similar to that reported for a New York City sample. Total rejection scores were significantly correlated with a number of demographic variables and with the treating physician's assessment of the degree of rejection, hostility and criticism of the respective family members. Physician's rating of emotional over-involvement did not correlate with PRS scores. Both PRS and treating physician's ratings correlated significantly with course of illness parameters. The findings and their implications are discussed in the context of expressed emotion (EE) research.

Adult↗

Proteinases of betaretroviruses bind single-stranded nucleic acids through a novel interaction module, the G-patch.

Retroviral proteinases (PRs) are essential for retrovirus infectivity but the mechanism of their activity regulation is poorly understood. We investigated possible involvement in this process of the C-terminal domain (CTD) of betaretroviral PRs. We found that the presence of CTD attenuates proteolytic activity of Mason-Pfizer monkey virus PR, while it does not significantly affect the activity of mouse intracisternal A-particle retrovirus PR. However, both PRs bind single-stranded nucleic acids through their CTDs that contain a novel binding motif, the G-patch, whose function is dependent on a single conserved tyrosine residue. Oligonucleotide binding to both PRs does not inhibit their proteolytic activity.

Amino Acid Motifs↗

Polygenic risk scores in the clinic: Health-system leaders and primary care providers weigh in.

PURPOSE: The fourth phase of the Electronic Medical Records and Genome Network is testing the return of 10 polygenic risk scores (PRS) across multiple clinics. Understanding the perspectives of health-system leaders and frontline clinicians can inform plans for implementation of PRS. METHODS: A total of 15 health-system leaders and 20 primary care providers took part in semistructured interviews. A descriptive thematic analysis was performed. RESULTS: Interviewees generally perceived PRS to have limited clinical utility, although they saw value in the potential to identify and act upon risks that are not otherwise detectable. Perceived potential drawbacks included negative psycho-emotional effects on patients, unnecessary follow-up, distracting from population health priorities, opportunity costs, and medicolegal liability. Implementation considerations included increased encounter time and the need for clinical practice guidelines, provider training, care coordination, and point-of-care resources. CONCLUSION: Participants generally expressed favorable views of precision medicine and also identified potential challenges to introducing PRS in clinical care. Implementation will require careful assessment of clinical utility vs usual care; ensuring that the benefit to be realized merits the time and resources required to interpret, return, and act on results and developing guidelines and other decision-making supports for providers and patients.

Humans↗

African-American adolescents' stress responses after the 9/11/01 terrorist attacks.

PURPOSE: To examine the impact of indirect exposure to the 9/11/01 attacks upon physical and emotional stress-related responses in a community sample of African-American (AA) adolescents. METHODS: Three months after the 9/11/01 terrorist attacks, 406 AA adolescents (mean age [SD] of 16.1 +/- 1.3 years) from an inner-city high school in Augusta, GA were evaluated with a 12-item 5-point Likert scale measuring loss of psychosocial resources (PRS) such as control, hope, optimism, and perceived support, a 17-item 5-point Likert scale measuring post-traumatic stress symptomatology (PCL), and measures of state and trait anger, anger expression, and hostility. Given the observational nature of the study, statistical differences and correlations were evaluated for effect size before statistical testing (5% minimum variance explained). Bootstrapping was used for testing mean differences and differences between correlations. RESULTS: PCL scores indicated that approximately 10% of the sample was experiencing probable clinically significant levels of post-traumatic distress (PCL score > 50). The PCL and PRS were moderately correlated with a r = .59. Gender differences for the PCL and PRS were small, accounting for 1% of the total variance. Higher PCL scores were associated with higher state anger (r = .47), as well as measures of anger-out (r = .32) and trait anger (r = .34). Higher PRS scores were associated only with higher state anger (r = .27). Scores on the two 9/11/01-related scales were not statistically associated (i.e., less than 5% of the variance explained) with traits of anger control, anger-in, or hostility. CONCLUSIONS: The majority of students were not overly stressed by indirect exposure to the events of 9/11/01, perhaps owing to the temporal, social, and/or geographical distance from the event. Those who reported greater negative impact appeared to also be experiencing higher levels of current anger and exhibited a characterologic style of higher overt anger expression.

Adolescent↗

In vitro synthesis of enzymatically active HIV-1 protease for rapid phenotypic resistance profiling.

BACKGROUND: Given the expanding antiretroviral therapy, inexpensive and fast HIV drug resistance assays are urgently needed. In this view, we have developed a novel phenotypic resistance test for HIV-1 protease inhibitors (PIs) based on recombinant expression of patient-derived HIV PR in Escherichia coli and subsequent enzymatic testing in a fluorescent readout. OBJECTIVES: To facilitate and expedite the test procedure, we have introduced coupled in vitro transcription/translation using a commercially available technology called RTS for producing enzymatically active HIV-1 protease (PR). STUDY DESIGN: We expressed one wild type PR and one highly resistant mutant starting from molecular clones as well as three patient-derived PRs. The amplified PR gene was either ligated into an expression vector or directly used as a template for the in vitro transcription/translation reaction. Enzymatic susceptibility data derived from in vitro expressed PRs were correlated to the respective results from E. coli expression and genotypic evaluation. RESULTS: All tested enzymes were obtained in sufficient quantities for complete resistance profiling to five PIs. The PRs required no purification prior to the enzymatic assay. Inhibition constants and enzymatic resistance factors compared well to corresponding data from PRs expressed in parallel in E. coli. Enzymatic resistance was in good agreement with the respective PR genotype. CONCLUSION: The presented in vitro transcription/translation system represents a novel approach for HIV PR expression starting from molecular clones or patient samples. Coupled with the enzyme-kinetic PR assay recently developed in our group it allows to sensitively quantify resistance to PIs. The test system is significantly less laborious and faster than currently available phenotypic drug resistance assays.

Cloning, Molecular↗

Anxiolytic activity of progesterone in progesterone receptor knockout mice.

Progesterone is an anxiolytic steroid that could play a role in the regulation of anxiety in women. However, the mechanism by which progesterone decreases anxiety is incompletely understood. Progesterone affects the function of the brain by two distinct mechanisms. Progesterone regulates reproductive behavior by activating intracellular progesterone receptors (PRs). In addition, progesterone is believed to influence neuronal activity through its conversion to allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of GABAA receptors. The extent to which the anxiolytic action of progesterone requires PRs is uncertain. In this study, we utilized PR knockout (PRKO) mice bearing a targeted null mutation of the PR gene that abrogates the function of both PR-A and PR-B subtypes to determine the requirement for PRs in the anxiolytic actions of progesterone. The absence of PR receptor protein expression in PRKO brain was confirmed by immunocytochemistry. In PRKO mice and their isogenic wild-type (WT) littermates, progesterone administration was associated with a dose-dependent rise in plasma allopregnanolone concentrations and corresponding anxiolytic effects in the elevated plus maze test. PRKO mice exhibited a greater anxiolytic response than WT animals although the allopregnanolone levels were similar in the two genotypes. Allopregnanolone also exhibited anxiolytic effects, but the magnitude of the response was similar in both genotypes. Pretreatment of PRKO mice with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone, completely prevented the anxiolytic activity of progesterone, but had no effect on the response to allopregnanolone, demonstrating that allopregnanolone (or other 5alpha-reduced metabolites of progesterone) accounts for the response to the parent steroid hormone. These results provide direct evidence that the anxiolytic action of progesterone does not require PRs. However, PR activation by progesterone may influence the anxiolytic response since PRKO mice were more sensitive to progesterone.

Analysis of Variance↗

Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study.

Intrathecal (IT) opioid therapy is a treatment alternative for patients with severe chronic non-malignant pain. Several uncontrolled retrospective and prospective outcome studies have suggested a benefit in chronic non-malignant pain patients, but uncertainties about patient selection in these studies weaken the results. This study evaluated long-term outcome of IT opioid therapy in chronic non-malignant pain prospectively, and included two comparative groups to improve understanding of selection criteria and relative severity of intrathecal pump recipients (PRs). The study subjects included 38 PRs while the comparative groups included 31 intrathecal candidates who either had an unsuccessful trial, or declined the IT therapy, and another group of 41 newly referred patients. The following data were analyzed at study entry, and at 6 monthly intervals for a 3-year period: Symptom Check List 90 (SLC-90), SF-36 Health survey, Beck Depression Inventory, McGill Pain Questionnaire (short form), Oswestry Disability Index, Pain Drawings and Pain rating on visual analogue scale. Data analysis suggests the study group of PRs had improvements in pain, mood, and function from baseline to 36 months. These same parameters improved among new referrals (less severe patients receiving conservative pain management) while non-recipients significantly worsened. Although PRs improved, they were still worse off at 36 months than new referrals were at baseline. The study showed that when patients with extremely severe pain problems are selected as pump candidates, they will likely improve with the therapy, but their overall severity of pain and symptoms still remains high.

Activities of Daily Living↗

The effect of embryo quality on subsequent pregnancy rates after in vitro fertilization.

OBJECTIVE: To determine if a simple morphological classification of embryos was predictive of subsequent pregnancy. DESIGN: Prospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS, PARTICIPANTS: Consecutive embryo transfer (ET) cycles (n = 206). INTERVENTIONS: Embryos were classified into three grades: (1) equal-size blastomeres with no fragmentation; (2) unequal-size blastomeres; and (3) evidence of fragmentation. MAIN OUTCOME MEASURES: Embryo quality, age, indication for IVF, and stimulation protocol were evaluated for their effect on pregnancy rates (PR's). RESULTS: In cycles in which the best embryo transferred was grade 3, 2, or 1, the clinical PRs per ET were 0% (0/11 cycles), 12.8% (6/47 cycles, P less than 0.05), and 21.8% (32/148 cycles, P less than 0.05), respectively. When one, two, or three or more grade 1 embryos were replaced, the clinical PRs per ET were 15.6%, 16.3%, and 40% (P less than 0.05), respectively. Using logistic regression, embryo quality (P = 0.0011) and patient's age (P = 0.0044) were the only variables that affected PRs. CONCLUSION: The transfer of more than two good quality embryos had a positive effect, patient's age had a negative effect on PRs after IVF-ET.

Age Factors↗

Cigarette smoking accelerates the development of diminished ovarian reserve as evidenced by the clomiphene citrate challenge test.

OBJECTIVE: To test whether the reduced fecundity in women who smoke cigarettes may be attributed to the accelerated development of diminished ovarian reserve. DESIGN: Retrospective evaluation of clomiphene citrate (CC) challenge tests in women from a general infertility population who did and did not smoke cigarettes (part 1) and retrospective evaluation of the impact of smoking on pregnancy rates (PRs) in IVF among women with normal ovarian reserve (part 2). SETTING: Large military tertiary care center. PATIENTS: Sixty-five women who smoked cigarettes and 145 women who did not smoke cigarettes in the general infertility population (part 1) and women undergoing IVF for strict tubal factor infertility with normal ovarian reserve who did (n = 29) and did not (n = 73) smoke (part 2). INTERVENTIONS: Clomiphene citrate challenge tests, composed of FSH levels on cycle days 3 and 10 with 100 mg of CC administered on cycle days 5 through 9. MAIN OUTCOME MEASURES: Comparison of the incidence of abnormal CC challenge test results between women who did and did not smoke, and comparison of peak E2 levels, number of mature follicles, number of mature oocytes retrieved, fertilization rates, and total and ongoing PRs. RESULTS: The incidence of diminished ovarian reserve was increased in women who smoked (8 of 65 [12.31%]) when compared with age-matched controls who did not smoke (7 of 145 [4.83%]). Among women with normal CC challenge tests who were undergoing IVF, there were no differences in peak E2 levels, the number of mature follicles, the number of mature oocytes retrieved, fertilization rates, or total and ongoing PRs. CONCLUSION: Women who smoke have an accelerated development of clinically detectable diminished ovarian reserve. Additionally, the fact that women who smoke cigarettes with normal ovarian reserve have ovarian responses and PRs that are equivalent to age-matched nonsmoking controls suggests that diminished ovarian reserve may be a principal mechanism reducing fecundity among women who smoke cigarettes.

Adult↗

Clomiphene citrate with intrauterine insemination: is it effective therapy in women above the age of 35 years?

OBJECTIVES: To evaluate the influence of female age on clomiphene citrate (CC) with IUI therapy and to compare the efficacy of this therapy between patients with ovulatory and anovulatory infertility. SETTING: A university fertility clinic. SUBJECTS: Six hundred sixty-four CC with IUI cycles from 290 women aged 22 to 48 years. MAIN OUTCOME MEASURES: Cumulative and clinical pregnancy rates (PRs). RESULTS: Both cumulative and clinical PRs declined substantially in women > 35 years when compared with those < or = 35 years. In addition, no difference in these parameters was noted between patients with ovulatory and anovulatory infertility diagnoses. The vast majority of pregnancies occurred within the first four treatment cycles, irrespective of age or ovulatory versus anovulatory infertility diagnoses. CONCLUSIONS: The age-related decline in clinical PR is most rapid beginning at the age of 35 years. For any given age group, CC with IUI therapy has similar cumulative and clinical PRs for both ovulatory and anovulatory infertility diagnoses. This therapy usually should not extend beyond four cycles. Couples should be counseled about the dramatic fall in PRs occurring beyond the age of 35 years.

Adult↗

Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome.

OBJECTIVE: To compare the efficacy of administration i.v. albumin to prevent severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing ovarian stimulation for IVF with a standard policy of cryopreserving all embryos and to assess the impact of the two methods of treatment on pregnancy rates (PRs). DESIGN: Prospective randomized study. SETTING: A tertiary referral center for assisted conception. PATIENTS: Twenty-six patients undergoing IVF treatment cycles who were considered to be at high risk of developing severe OHSS on the basis of their serum E2 concentrations on the day of hCG administration and the number of oocytes collected. INTERVENTION: In group 1 (n = 13) all the generated embryos were cryopreserved to be transferred subsequently in hormonally manipulated cycles. In group 2 (n = 13) patients received IV infusions of albumin on the day of oocyte retrieval and 5 days later. Patients in group 2 had transfers of fresh embryos. MAIN OUTCOME MEASURES: The total dosage of hMG used, total number of follicles developed, number of follicles > 14 mm in diameter, serum E2 concentrations and endometrial thickness on day of hCG administration, number of oocytes retrieved, number and quality of embryos generated, PRs per cycle commenced, and onset and degree of any OHSS developed. RESULTS: There were no significant differences in the above parameters between the two groups, except for PRs that were significantly higher in patients who had all embryos cryopreserved (38.6% versus 0%). CONCLUSION: The policy of cryopreserving all generated embryos appears as effective as the administration of i.v. albumin in preventing OHSS in high-risk patients and produces significantly higher PRs.

Adult↗

Transfer of cryopreserved embryos improved pregnancy rates in patients with damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test.

OBJECTIVE: To compare the pregnancy rates (PRs) after transfer of cryopreserved embryos in patients who have damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test to those without this defect. DESIGN: Prospective clinical study. SETTING: University-associated IVF center. PATIENTS: Fifty-four patients enrolled in a matched prospective study to evaluate the effects of low HOS scores (<50%) on PRs after IVF-ET were followed to determine the PR after transfer of cryopreserved embryos. MAIN OUTCOME MEASURE: Clinical PRs and implantation rates. RESULTS: Fourteen patients with low hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved for clinical pregnancies for a PR per cycle of 19.0% and an implantation rate of 7.1%. Twelve patients with normal hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved five preganancies for a clinical PR per cycle of 23.8% and an implantation rate of 9.3%. CONCLUSION: Previous studies have demonstrated an adverse effect of low hypo-osmotic swelling test scores on PRs after IVF-ET despite normal fertilization. This adverse effect was not found in the transfer of cryopreserved embryos from males with hypo-osmotic swelling test scores. Further investigation is required to determine how cryopreservation improves the chances of implantation of these embryos.

Cell Membrane↗

Antiphospholipid antibodies and pregnancy rates and outcome in in vitro fertilization patients.

OBJECTIVE: To determine the relationship between antiphospholipid antibodies and pregnancy rates (PRs) and outcome among IVF patients. DESIGN: Prospective collection of all serum samples with assays for immunoglobulin G (IgG), IgA, and IgM antibodies for anticardiolipin, antiphosphatidyl serine, antiphosphatidyl ethanolamine, antiphosphatidyl choline, antiphosphatidyl inositol, antiphosphatidyl glycerol, and antiphosphatidic acid being done following completion of all treatment cycles. SETTING: A tertiary care teaching hospital. PATIENT(S): Seven hundred ninety-three patients attempting to conceive through IVF. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) and pregnancy loss rates relative to each of the various antiphospholipid antibodies that were measured. RESULT(S): There were 528 pregnancies for an overall PR of 66%. Pregnancy rates were equal among patients with positive and negative antiphospholipid antibodies for each of the 21 measured antibodies. Use of receiver operator characteristic curves and logistic regression further confirmed that there was no relationship between PRs or outcome based on antiphospholipid antibodies for any definable threshold value. CONCLUSION(S): Elevated antiphospholipid antibody levels are not associated with any change in PRs or pregnancy loss rates in patients attempting to conceive through IVF.

Adult↗

Clomiphene citrate ovulation induction in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone versus human chorionic gonadotropin timing.

OBJECTIVE: To evaluate the clinical pregnancy rates (PRs) in anovulatory, male factor, and unexplained infertility using clomiphene citrate (CC) with an IUI and to evaluate the difference in PRs between urinary LH testing and hCG administration for timing of the IUI. DESIGN: Retrospective clinical study. SETTING: Academic, tertiary care fertility center. PATIENT(S): One hundred thirty-eight couples (432 cycles) undergoing IUI with CC ovulation induction as a treatment for unexplained, anovulatory, or male factor infertility were selected. INTERVENTION(S): All women with unexplained or male factor infertility received CC at a dose of 50 mg/d, and those with anovulation received CC at a dose ranging from 50 to 200 mg/d. All women in the study received a single IUI either the morning after a urinary LH surge or 36 to 38 hours after an evening hCG injection. MAIN OUTCOME MEASURE(S): Clinical PR. RESULT(S): There were no differences in the clinical PRs between LH testing or hCG administration in any of the three groups. Clinical PRs were extremely low in the male factor infertility group regardless of the timing used. CONCLUSION(S): These data suggest that the success of IUI with CC is not dependent on the method used to establish the timing for the IUI. In couples undergoing IUI with CC, the use of urinary LH testing may result in lower costs by reducing patient visits and the midcycle ultrasound.

Adult↗

Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm.

OBJECTIVE: To compare the fertilization rates and pregnancy rates (PRs) in intracytoplasmic sperm injection (ICSI) using sperm from ejaculates of normal and abnormal semen, epididymal sperm, and testicular sperm of obstructive and nonobstructive azoospermic patients. DESIGN: Retrospective study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Three hundred fifty patients underwent 366 ICSI cycles. INTERVENTION(S): ICSI, epididymal sperm aspiration, and testicular biopsy. MAIN OUTCOME MEASURE(S): Fertilization rates and PRs. RESULT(S): Patients were divided into five groups according to the quality and source of sperm. Patients in group 1 underwent 102 cycles of ICSI using ejaculated abnormal semen, group 2 underwent 44 cycles using epididymal sperm, group 3 underwent 82 cycles using testicular sperm from obstructive azoospermia, group 4 underwent 80 cycles using testicular sperm from nonobstructive azoospermia, and group 5 underwent 58 cycles using normal semen. There was no significant difference in the fertilization rates and PRs among groups 1, 2, and 3. In group 4, the fertilization rate and PR were significantly lower than in all other groups. In group 5, the fertilization rate was significantly higher than in all other groups. CONCLUSION(S): The fertilizing ability of sperm in ICSI is highest with normal semen and lowest with sperm extracted from a testicular biopsy in nonobstructive azoospermia. There was no significant difference in fertilization rates and PRs between ejaculated sperm of different parameters and surgically retrieved sperm in obstructive azoospermia.

Adult↗

Comparison of blastocyst transfer with day 3 embryo transfer in similar patient populations.

OBJECTIVE: To compare implantation and pregnancy rates (PRs) achieved with blastocyst transfer (BT) and day 3 ET in similar patient populations. DESIGN: Retrospective analysis. SETTING: Academic infertility center. PATIENT(S): One hundred consecutive patients <40 years undergoing IVF, each with more than three eight-cell embryos on day 3. INTERVENTION(S): Patients used their own eggs for IVF or IVF and intracytoplasmic sperm injection. Embryos were cultured in P1 medium (Irvine Scientific, Santa Ana, CA) until day 3, when they were either transferred or, in the case of embryos for BT, incubated in Blastocyst Medium (Irvine Scientific), followed by transferring on day 5. MAIN OUTCOME MEASURE(S): Implantation and PRs. RESULT(S): There were no statistically significant differences in patient age, FSH level, or number of oocytes or zygotes. The BT group had fewer embryos transferred (mean, 2.4) compared with the day 3-ET group (mean, 4.6). The viable PR (cardiac activity at 6-7 weeks was considered indicative of a viable pregnancy) was higher with BT (68%, 34/50) than with day 3 ET (46%, 23/50). The implantation rate was increased with BT (47%, 56 sacs/120 embryos) compared with day 3 ET (20%, 46 sacs/231 embryos). CONCLUSION(S): The BT group in our study had higher implantation and PRs compared with the day 3-ET group. Better embryo selection, improved embryo-uterine synchrony, and decreased cervical mucus on day 5 may have accounted for the enhanced outcome. Our data support the use of BT to limit the number of embryos transferred while improving PRs.

Adult↗

Phosphoribosylpyrophosphate synthetase and the regulation of phosphoribosylpyrophosphate production in human cells.

between purine nucleoside diphosphate inhibition and inorganic phosphate (Pi) activation; and intracellular concentration of the PRS1 isoform. The operation of additional determinants of rates of PRPP synthesis in human cells is suggested by: (1) multiple PRS isoforms with distinctive physical and kinetic properties; (2) nearly immediate activation of intracellular PRPP synthesis in response to mitogens, growth-promoters, and increased intracellular Mg2+ concentrations; (3) tissue-specific differences in PRS1 and PRS2 transcript and isoform expression; and (4) reversible association of PRS subunits with one another and/or with PRS-associated proteins (PAPs), as a result of which the catalytic and perhaps regulatory properties of PRS isoforms are modified.

Amino Acid Sequence↗

Anti-sense oligonucleotides, for progestin receptors in the VMH and glutamic acid decarboxylase in the VTA, attenuate progesterone-induced lordosis in hamsters and rats.

Immunocytochemical (ICC) staining for progesterone (P) receptors (PRs) and glutamic acid decarboxylase (GAD), the enzyme responsible for GABA production, reveal that there are many PRs in the ventral medial hypothalamus (VMH) and many GAD containing neurons in the ventral tegmental area (VTA). To investigate P's action on lordosis in the VMH and VTA, anti-sense oligos specific to PRs and GAD(65&67) were intracerebrally infused into the VMH and VTA of 24 ovariectomized hamsters and 40 ovariectomized rats. Estradiol benzoate (2 microg) primed hamsters and rats were infused to the VMH and the VTA with either PR (250 ng/1.0 microl infusion) or GAD (500 ng/1.0 microl infusion) anti-sense oligos, their scramble controls, or saline vehicle at hour 0 and again at hour 24. At hr 44, rodents were subcutaneously injected with P (500 microg) and were tested for sexual receptivity with a male 4 h later. There were significant reductions in lordosis of hamsters and rats following PR anti-sense infusions to the VMH compared to scrambled or vehicle control infusions. Effects of PR anti-sense to the VMH were not different from combined VMH and VTA PR anti-sense infusions; however, VMH infusions reduced lordosis compared to VTA-only anti-sense infusions. GAD anti-sense infusions reduced lordosis when infused into the VTA, compared to scrambled or saline vehicle infusions. Lordosis responsiveness following VTA GAD anti-sense infusions was not different from combined VMH and VTA infusions, but VTA infusions of GAD anti-sense reduced lordosis compared to VMH-only anti-sense infusions. These data suggest that in the VMH, PRs are important for P-facilitated lordosis, whereas in the VTA, GABAergic neurons may be an important substrate for mediating P's actions on lordosis of rodents.

Animals↗