The Origins of Neocortex: Connections and Lamination as Distinct Events in Evolution

In the nonmammalian telencephalon, there are neuronal populations corresponding to cell groups in the neocortex of mammals in terms of connections, single unit-responses, chemical content, and functions. Some of these populations in nonmammals, however, are organized in a nonlaminar, rather than laminar fashion. These observations may prompt a reassessment of the functional roles of lamination and the evolutionary origins of the mammalian neocortex. Thus, the role of neural circuits and laminar organization can be differentiated in order to understand the cognitive functions of the neocortex. Moreover, the origins of neocortex can be separable into the precursors of nonlaminar and laminar regions

Sections, Medications Discovery Research Branch, Intramural Research Program, Department of Health and Human Services

ABSTRACT Sigma receptor (R) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in selfadministration procedures. However, the R antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dosedependently decreased the maximal rates of cocaine selfadministration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective R antagonists in their dual affinities for Rs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and R antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both Rs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2␤-carbomethoxy-3␤-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and R antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of cocaine, neither rimcazole analogs nor typical R antagonists (NE-100 and AC927) maintained responding above control levels across a wide range of doses. These findings suggest that the unique effects of rimcazole analogs are due to dual actions at the DAT and Rs and that a combined target approach may have utility in development of medical treatments for cocaine abuse

Stress system development from age 4.5 to 6: Family environment predictors and adjustment implications of HPA activity stability versus change

ABSTRACT: This study addressed early calibration of stress systems by testing links between adversity exposures, developmental stability of hypothalamic-pituitary-adrenal (HPA) axis activity, and behavior problems in a sample of adopted children. Families (n ¼ 200) were assessed when the child was 9, 18, and 27 months, 4.5 and 6 years to collect adversity information-parent psychopathology, stress, financial need, and home chaos. Morning and evening cortisol samples at the final two assessments indexed child HPA activity, and parentreported internalizing and externalizing at the final assessment represented child behavior outcomes. Increases in cumulative adversity from 4.5 to 6 related to higher child morning cortisol, whereas age six cumulative adversities related to lower, unstable child evening cortisol. Examination of specific adversity dimensions revealed associations between (1) increasing home chaos and stable morning cortisol, which in turn related to internalizing problems; and (2) high parental stress and psychopathology and lower, unstable evening cortisol, which in turn related to externalizing problems. ß 2013 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1-15, 2013

JPET #185025 Decreases in Cocaine Self Administration with Dual Inhibition of the Dopamine Transporter and σ Receptors

Abstract: 241 words Introduction: 678 word