The organization of behavior: A neuropsychological theory

The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges. The re-establishment and maintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity. Limbic regions that are responsible for regulating stress responses intersect with circuits that are responsible for memory and reward, providing a means to tailor the stress response with respect to prior experience and anticipated outcomes.

Neural regulation of endocrine and autonomic stress responses.

The chronic mild stress (CMS) model of depression has high validity but has in the past been criticized for being difficult to replicate. However, a large number of recent publications have confirmed

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects

Stress is a well-known risk factor in the development of addiction and in addiction relapse vulnerability. A series of population-based and epidemiological studies have identified specific stressors and individual-level variables that are predictive of substance use and abuse. Preclinical research also shows that stress exposure enhances drug self-administration and reinstates drug seeking in drug-experienced animals. The deleterious effects of early life stress, child maltreatment, and accumulated adversity on alterations in the corticotropin releasing factor and hypothalamic-pituitary-adrenal axis (CRF/HPA), the extrahypothalamic CRF, the autonomic arousal, and the central noradrenergic systems are also presented. The effects of these alterations on the corticostriatal-limbic motivational, learning, and adaptation systems that include mesolimbic dopamine, glutamate, and gamma-amino-butyric acid (GABA) pathways are discussed as the underlying pathophysiology associated with stress-related risk of addiction. The effects of regular and chronic drug use on alterations in these stress and motivational systems are also reviewed, with specific attention to the impact of these adaptations on stress regulation, impulse control, and perpetuation of compulsive drug seeking and relapse susceptibility. Finally, research gaps in furthering our understanding of the association between stress and addiction are presented, with the hope that addressing these unanswered questions will significantly influence new prevention and treatment strategies to address vulnerability to addiction.

Chronic Stress, Drug Use, and Vulnerability to Addiction

Gender differences in cocaine use and treatment response

It is now well-documented that exposures to uncontrollable (inescapable and unpredictable) stress in adulthood can have profound effects on brain and behavior. Converging lines of evidence from human and animal studies indicate that stress interferes with subsequent performances on a variety of hippocampal-dependent memory tasks. Animal studies further revealed that stress impedes ensuing induction of long-term potentiation (LTP) in the hippocampus. Because the hippocampus is important for key aspects of memory formation and because LTP has qualities congruent to an information storage mechanism, it is hypothesized that stress-induced modifications in hippocampal plasticity contribute to memory impairments associated with stress. Recent studies provide evidence that the amygdala, a structure important in stress- and emotion-related behaviors, plays a necessary role in the emergence of stress-associated changes in hippocampal LTP and memory. Early life stress also alters hippocampal plasticity and memory in a manner largely consistent with effects of adult stress exposure. This review focuses on endocrine-system-level mechanisms of stress effects in the hippocampus, and how stress, by altering the property of hippocampal plasticity, can subsequently influence hippocampal memory.

Stress effects in the hippocampus: Synaptic plasticity and memory

Objective A "best estimate" diagnosis is one made by expert clinicians on the basis of diagnostic information from direct interview conducted by another clinician plus information from medical records and from reports of family members. The authors address the question of whether the best estimate procedure can enhance the classification of psychiatric diagnoses of subjects who are interviewed directly. Method Four hundred seventy-five subjects were interviewed directly: 201 opiate-addicted probands who sought treatment from a university-based clinic and 274 of their spouses and/or first-degree relatives. Subjects were interviewed by trained clinical assessors using the Schedule for Affective Disorders and Schizophrenia and classified according to Research Diagnostic Criteria. Two psychologists independently diagnosed the same subjects by applying the best estimate procedure. Lifetime rates of major and minor depressive disorder, antisocial personality, alcoholism, and drug abuse were calculated. The rates of diagnoses made on the basis of direct interviews alone were compared with the rates of diagnoses made according to the best estimate procedure. Results Higher rates of diagnoses of all four disorders were made when the best estimate procedure was applied than when direct interview alone was used; the best estimate procedure also resulted in a minimal rate of false positives. Conclusions The higher rate of diagnoses based on the best estimate procedure may represent an enhancement in the accuracy of psychiatric diagnoses or an increase in erroneous diagnoses. The authors consider the second possibility less likely.

Sensitivity of psychiatric diagnosis based on the best estimate procedure.

Enhanced acquisition of cocaine self-administration in adult rats with neonatal isolation stress experience

Current research suggests there are genetic differences in susceptibility to drug abuse. One way to examine this relationship is to study inbred strains, such as Lewis (LEW) and Fischer 344 (F344) rats, that show differential biochemical and behavioral effects in response to psychoactive drugs. In the present study several behavioral effects of cocaine were compared in these strains, including conditioned place preference (CPP), conditioned taste aversion and locomotor activity. Cocaine CPP was greater in LEW rats than in F344 rats. In contrast, cocaine conditioned taste aversion did not differ between LEW and F344 rats, or did the locomotor activity levels seen after the first cocaine administration. LEW rats, however, showed enhanced locomotor activity to repeated cocaine administrations at all doses tested, an effect not seen in F344 rats. These data suggest that differences in the development of cocaine CPP in LEW and F344 rats are not due to differences in detection of or in inability to condition to cocaine. Rather, these differences in CPP may reflect strain differences in the response to repeated cocaine administrations and may be related to previously observed biochemical differences between the two rat strains.

Fischer and Lewis rat strains show differential cocaine effects in conditioned place preference and behavioral sensitization but not in locomotor activity or conditioned taste aversion.

Therese A. Kosten

Papers

Gender differences in cocaine use and treatment response

Stress effects in the hippocampus: Synaptic plasticity and memory

Sensitivity of psychiatric diagnosis based on the best estimate procedure.

Enhanced acquisition of cocaine self-administration in adult rats with neonatal isolation stress experience

Fischer and Lewis rat strains show differential cocaine effects in conditioned place preference and behavioral sensitization but not in locomotor activity or conditioned taste aversion.