Some people who repeatedly use stimulant drugs, such as amphetamine (AMPH), develop an AMPH-induced psychosis that is similar to paranoid schizophrenia. There has been, therefore, considerable interest in characterizing the effects of chronic stimulant drug treatment on brain and behavior in non-human animals, and in developing an animal model of AMPH psychosis. A review of this literature shows that in non-human animals chronic AMPH treatment can produce at least two different syndromes, and both of these have been proposed as animal models of AMPH psychosis. The first syndrome is called 'AMPH neurotoxicity', and is produced by maintaining elevated brain concentrations of AMPH for prolonged periods of time. AMPH neurotoxicity is characterized by what has been termed 'hallucinatory-like' behavior, which occurs in association with brain damage resulting in the depletion of striatal DA and other brain monoamines. The second syndrome is called 'behavioral sensitization', and is produced by the repeated intermittent administration of lower doses of AMPH. Behavioral sensitization is characterized by a progressive and enduring enhancement in many AMPH-induced behaviors, and is not accompanied by brain damage or monoamine depletion. It is argued that the changes in the brain and behavior associated with the phenomenon of behavioral sensitization provide a better 'model' of AMPH psychosis than those associated with AMPH neurotoxicity. Much of the review involves a critical analysis of hypotheses regarding the biological basis of behavioral sensitization. Research on this question has focused on mesotelencephalic DA systems, and suggestions that behavioral sensitization is accompanied by: an increase in postsynaptic DA receptors; an increase in DA synthesis; an increase in DA utilization and/or release; and a decrease in DA autoreceptors, are evaluated. It is concluded that there is not convincing evidence for an increase in postsynaptic DA receptors or in DA synthesis in animals sensitized to AMPH. In contrast, there is strong evidence to support the notion that behavioral sensitization is due to enhanced mesotelencephalic DA release, especially upon re-exposure to the drug. The evidence that this enhancement in DA release is due to autoreceptor subsensitivity was found to be equivocal, and therefore other hypotheses should be entertained. Lastly, evidence is discussed in support of the idea that behavioral sensitization is not unique to the psychopharmacology of stimulant drugs, but may be produced by many environmental stimuli that directly or indirectly activate brain catecholamine systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Sex differences are present for all of the phases of drug abuse (initiation, escalation of use, addiction, and relapse following abstinence). While there are some differences among specific classes of abused drugs, the general pattern of sex differences is the same for all drugs of abuse. Females begin regularly self-administering licit and illicit drugs of abuse at lower doses than do males, use escalates more rapidly to addiction, and females are at greater risk for relapse following abstinence. In this review, sex differences in drug abuse are discussed for humans and in animal models. The possible neuroendocrine mechanisms mediating these sex differences are discussed.

Female and male brains differ. Differences begin early during development due to a combination of genetic and hormonal events and continue throughout the lifespan of an individual. Although researchers from a myriad of disciplines are beginning to appreciate the importance of considering sex differences in the design and interpretation of their studies, this is an area that is full of potential pitfalls. A female's reproductive status and ovarian cycle have to be taken into account when studying sex differences in health and disease susceptibility, in the pharmacological effects of drugs, and in the study of brain and behavior. To investigate sex differences in brain and behavior there is a logical series of questions that should be answered in a comprehensive investigation of any trait. First, it is important to determine that there is a sex difference in the trait in intact males and females, taking into consideration the reproductive cycle of the female. Then, one must consider whether the sex difference is attributable to the actions of gonadal steroids at the time of testing and/or is sexually differentiated permanently by the action of gonadal steroids during development. To answer these questions requires knowledge of how to assess and/or manipulate the hormonal condition of the subjects in the experiment appropriately. This article describes methods and procedures to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.

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Summary The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone, leptin, modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA, and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.

This review discusses alcohol/other drug addiction as both a sociocultural and biological phenomenon. Sex differences and gender are not solely determined by biology, nor are they entirely sociocultural. The interactions among biological, environmental, sociocultural and developmental influences result in phenotypes that may be more masculine or more feminine. These gender-related sex differences in the brain can influence the responses to drugs of abuse, progressive changes in the brain after exposure to drugs of abuse and whether addiction results from drug-taking experiences. The basic laboratory evidence for sex differences in addiction is discussed within the context of four types of sex/gender differences.

The literatures on hormone changes at adolescence, hormonal influences on moods and behavior in nonhuman animals and adult humans, and mood and behavioral changes at adolescence and the small but burgeoning literature on hormonal influences at adolescence are examined. The focus is on moods and behaviors often identified as typically adolescent (e.g., mood lability, mood intensity, irritability, conflict with parents) and the primary hormones of puberty (i.e., the adrenal androgens, gonadotropins, and sex steroids). Through an integration of these literatures evidence is assessed for specific hormone-mood and hormone-behavior associations, as well as for more general types of hormone-outcome relations that transcend specific hormones or outcomes. Non-biological factors that appear to be important in moderating the role of hormones in adolescent moods and behavior are identified. Implications for the design of future studies in this area are detailed.