Some behavioral effects of repeated d-amphetamine administrations

Effects of daily administrations of d-amphetamine were studied on key peck responses of pigeons maintained under a multiple fixed-interval 2-min, fixed-ratio 30-responseschedule. Under the fixed-interval schedule, a pause was followed by a transition to increasing rates of responding until food presentation. Under the fixed-ratio schedule, higher sustained rates of responding were maintained. Low to intermediate doses (0.3-1.0 mg/kg) of d-amphetamine changed the temporal patterns and occasionally increased rates of responding under the fixed-interval schedule. Higher doses decreased rates of responding under bothschedules. With daily injections of 1.0 mg/kg d-amphetamine prior to experimental sessions, the effects of this dose on rates and patterns of responding were attenuated, and d-anphetamine dose-effect curves were shifted to the right, primarily under the fixed-ratio schedule. Similar results were obtained with daily presession injections of 5.6 mg/kg d-amphetamine in a second group of pigeons, except that rates of responding under both schedules were decreased by this daily dose, and did not return completely to control values with repeated injections. In a third group of pigeons, 1.0 mg/kg d-amphetamine administered daily, after experimental sessions, did not alter dose-effect functions for d-amphetamine. In a second experiment, pigeons were trained to peck one response key when given 1.0 mg/kg d-amphetamine and a different key when given presession water injections. Increasing doses of d-amphetamine produced incresing percentages of d-amphetamine-key responses. Repeated administration of 5.6 mg/kg d-amphetamine shifted these dose-effect functions to the right one-half log unit. Results suggested that decreases in reinforcement frequency are not a necessary condition for the development of behavioral tolerance to d-amphetamine.     

Down-Regulation of Estrogen Receptor Immunoreactivity by 17β-estradiol in the Guinea Pig Forebrain

Low amplitude pulses of estradiol-17β (E₂-17β) are more effective than large single bolus injections or constant exposure to E₂-17β in inducing progesterone-facilitated sex behavior in female rats and guinea pigs. The present study examined whether the increased responsiveness to E₂-17β is due to an increase in the number of estrogen receptors in the estrogen receptor rich areas of the hypothalamus and amygdala. Initial studies examined the rapid effects (20 min) of a high dose of E₂-17β (50 μg) on estrogen receptor immunostaining using either the H222 antibody or the ER 21 antiserum. ER 21 immunostaining was not affected by the E₂-17β treatment suggesting that it binds to both occupied and unoccupied estrogen receptors. Therefore the ER 21 antiserum was used to characterize the regulation of estrogen receptor immunoreactivity (ER-IR) by E₂-17β. ER-IR was examined for 48 h and serum E₂-17β for 24 h following a 2 μg s.c. injection of E₂-17β (a dose similar to that used in multiple pulse paradigms). Serum E₂-17β peaked 15 to 30 min following the injection and returned to baseline values by 1 h. In all but one area maximal suppression of ER-IR occurred at 12 h. In summary, 1) decreases in estrogen receptor immunoreactivity following E₂-17β are consistent with studies in which estrogen receptors were assayed by binding assays and estrogen receptor mRNA was determined by in situ hybridization; 2) the ER 21 antiserum is able to detect both occupied and unoccupied estrogen receptors and 3) H222 immunoreactivity is influenced by the presence of E₂-17β, so that the level of H222-IR is a reflection of ligand/receptor binding dynamics. The data suggest that up-regulation of estrogen receptors does not account for the increase in behavioral sensitivity which is observed following multiple pulses of E₂-17β.     

Decomposing Area of Residence Differences in Multiple Regression Studies: The Relative Contributions of Independent Variables and Model Coefficients

When rural/urban differences are found in health status or health care use, it is often desirable to identify those factors (such as age, social structure, income, etc.) that influence such differences. To this end, researchers often test rural/urban differences in age, social structure, income, etc., for statistical significance. Also, researchers commonly perform multivariate analyses (such as multiple regressions) to examine rural-urban differences in the influence of various independent variables on the dependent variable of interest. Frequently, researchers discover: (1) statistically significant rural/urban differences in the independent variables (such as age, social structure, income, etc.) and (2) statistically significant rural/urban differences in the effects of these independent variables (i.e., statistically significant rural/urban differences in regression coefficients). The analysis typically stops here, without addressing the relative contributions of (1) and (2) to the rural/urban differences in the dependent variable. This paper argues that the relative contributions of (1) and (2) have important implications for the way policy-makers address rural health problems. This paper presents a method for assessing the relative contributions of differences in the independent variables and differences in regression coefficients to observed differences in the dependent variable, and illustrates the application of the method by analyzing rural/urban differences in the risk of institutionalization.