Evaluation of estradiol administration on the discriminative-stimulus and subject-rated effects of d-amphetamine in healthy pre-menopausal women.

Accumulating evidence suggests that estradiol might be responsible for the enhanced response to psychostimulants sometimes observed in females. In this study, 10 healthy pre-menopausal women who were using oral, hormone-based birth control learned to discriminate 15 mg/70 kg oral d-amphetamine from placebo. Once a discrimination criterion was met (i.e., >or=80% correct responding at the final time point for five consecutive sessions), a range of doses of oral d-amphetamine (0, 3.125, 7.5 and 15 mg/70 kg) was tested alone and in combination with sublingual estradiol (0 and 0.25 mg). Test sessions were conducted during the oral contraception placebo phase when levels of both estradiol and progesterone were at their lowest. d-Amphetamine functioned as a discriminative stimulus and produced prototypical stimulant effects (e.g., increased positive subject-rated drug effects, elevated cardiovascular measures). Estradiol enhanced the discriminative-stimulus effects of the low dose, but not higher doses of d-amphetamine. Estradiol also enhanced d-amphetamine effects on a subset of self-report ratings (i.e., VAS Like Drug and total score on the Stimulant subscale of the Adjective-Rating Scale). These findings provide limited support for the notion that estradiol increases sensitivity to the psychostimulant effects of drugs such as d-amphetamine.

Vocational outcomes after brain injury in a patient population evaluated for Life Care Plan reliability.

This retrospective cohort study examined the vocational outcomes in forty-four traumatically brain injured patients. Patient files selected were limited to those who were seen for the development of an original Life Care Plan and were subsequently seen at least once for a complete update of that plan. Patients who were retired at the time of the brain injury were excluded. Each participant was actively involved in litigation at the time of the initial evaluation as well as at the time of his or her update evaluation. Traumatic brain injury resulted from various etiologies. Vocational outcomes were analyzed in relation to severity of injury, age at onset, gender and education. Vocational outcome was reported as a return to work, supported employment, return to school or training or permanent total disability. Twenty-one patients were classified as permanent-total disabilities. Twenty-three returned to work, supported employment, or were successfully in school and expected to return to work. This 52% rate of vocational or school participation is particularly noteworthy since all cases were actively in litigation. A significant trend was found for severity of injury, and level of education, but not for age at onset or gender. These factors are discussed in relation to the subjects' participation in third party civil litigation and implications for Life Care Planning.

Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism.

BACKGROUND: HIV Associated Dementia (HAD) is a common complication of human immunodeficiency virus (HIV) infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein) have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, to produce a significant synergistic neurotoxicity. Using this model system, the neuroprotective potential of gonadal steroids was investigated. RESULTS: 17beta-Estradiol (17beta-E2), but not 17alpha-estradiol (17alpha-E2), was protective against this combined neurotoxicity. Progesterone (PROG) afforded limited neuroprotection, as did dihydrotestosterone (DHT). The efficacy of 5alpha-testosterone (T)-mediated neuroprotection was robust, similar to that provided by 17beta-E2. In the presence of the specific estrogen receptor (ER) antagonist, ICI-182,780, T's neuroprotection was completely blocked. Thus, T acts through the ER to provide neuroprotection against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated concentration-dependent neuroprotection, possibly attributable to cholesterol's serving as a steroid hormone precursor in neurons. CONCLUSION: Collectively, the present data indicate that cocaine has a robust interaction with the HIV proteins gp120 and Tat that produces severe neurotoxicity, and this toxicity can be blocked through pretreatment with ER agonists.