Administration of progesterone produces mild sedative-like effects in men and women.

The goal of this study was to investigate the behavioral and subjective effects of a single dose of progesterone in men and women. Certain metabolites of progesterone (e.g., allopregnanolone) are potent positive allosteric modulators of GABA(A) receptors, and produce sedative-like effects in laboratory animals. This study was designed to examine the acute effects of these neurosteroids in humans. Women (n=7) in their early follicular phase and men (n=10) received intramuscular injections of progesterone (200 mg) or placebo. Dependent measures included plasma levels of progesterone and allopregnanolone, self-report measures of mood and subjective effects and behavioral measures of psychomotor performance. Plasma concentrations of progesterone and allopregnanolone increased reliably and with little intersubject variability after drug administration, and levels were similar in men and women. Administration of progesterone produced small, delayed increases in heart rate and feelings of fatigue, and it impaired smooth eye pursuit. These results suggest that, although the effects are modest and not simply related to plasma concentrations, progesterone and its metabolites can produce sedative-like effects in both men and women.

Effects of acute social stress on alcohol consumption in healthy subjects.

BACKGROUND: There has been renewed interest in interactions between stress and use of drugs and alcohol. Although there is evidence that stress increases drug use in human drug users and in laboratory animals, the processes by which stress affects drug-motivated behavior are not understood. Here we examined the effects of an acute social stressor (performing a mental arithmetic task in front of an audience) on consumption of ethanol or placebo beverages in healthy social drinkers. METHODS: Thirty-seven men and women, ages 21-35, were randomly assigned to a placebo (n = 15) or ethanol group (n = 22). Subjects participated in two sessions, one with stress (Trier Social Stress Test) the other without stress. In each session, immediately after the stress or no-stress period, subjects consumed the first dose (placebo or 0.3 g/kg of ethanol for men or 0.2 g/kg for women). Then, subjects were allowed to choose up to six more beverages (0.1 g/kg each for the ethanol group or placebo beverages for the placebo group). Measures included percentage of beverage consumed, salivary cortisol level, heart rate, blood pressure, and subjective ratings of mood and drug effect. RESULTS: Subjects in both the placebo and ethanol groups consumed significantly more of their beverages after stress, compared to no stress. Stress increased anxiety, uneasiness, and produced some stimulant-like effects and, in the ethanol group, it dampened some of the acute subjective effects of ethanol. The direct physiologic and mood effects of the stress were fairly short-lived. CONCLUSIONS: It is concluded that acute stress may produce a modest increase in alcohol consumption in healthy, nonproblem social drinkers but that this increase is not directly related to the pharmacological effects of the drug. Nonpharmacological factors may include expectancies, thirst, or nonspecific facilitation of ongoing behaviors.

Environmental complexity has different effects on the structure of neurons in the prefrontal cortex versus the parietal cortex or nucleus accumbens.

Complex housing has been used widely as a model of experience-dependent change. Animals housed in complex environments typically show synaptogenesis throughout the sensory and motor cortex as well as the striatum and hippocampus, and thus it is generally assumed that such changes are likely to be found throughout the cerebrum. The purpose of the present study was to determine whether persistent alterations of dendritic morphology would be found in two regions that had previously not been examined, namely, the medial prefrontal region (Cg3) and nucleus accumbens (NAcc). The results show that housing female rats in complex environments for 3.5 months increased dendritic arborization on medium spiny neurons in the NAcc and on pyramidal cells in the somatosensory cortex (Par 1), but not in Cg3. Environmental complexity increased spine density in all three areas, however. The failure to find increased dendritic length or branching in Cg3 was unexpected. Thus, the data suggest that complex housing may not engage prefrontal neurons in the same manner as neurons in sensory or motor areas. It appears that complex housing may not produce generalized changes in cerebral morphology. The data further suggest that it is prudent to measure both dendritic length and spine density in studies of experience-dependent effects on synaptic plasticity.

Effects of stress and alcohol on subjective state in humans.

BACKGROUND: There is increasing evidence that stress and hypothalamic-pituitary-adrenal axis activation interact with drugs of abuse and influence drug-taking behaviors. Both studies with laboratory animals and survey data with alcohol users suggest that acute or chronic stressful events increase alcohol intake. One mechanism for the increase in alcohol intake may be that stress alters the subjective effects produced by the drug in ways that enhance the reinforcing properties of alcohol. Therefore, in this study we determined whether an acute social stressor alters subjective responses to ethanol in humans. The stressor was a modified version of the Trier Social Stress Test, an arithmetic task that increases cortisol levels. METHODS: Twenty male volunteers participated in two laboratory sessions, in which they performed the Trier Social Stress Test on one session and no task on the other session, immediately before consuming a beverage that contained ethanol (0.8 g/kg in juice) or placebo (juice alone). Eleven subjects received ethanol on both sessions, and nine subjects received placebo on both sessions. Primary dependent measures were self-report questionnaires of mood states. Salivary levels of cortisol were obtained to confirm the effectiveness of the stress procedure. RESULTS: Stress alone produced stimulant-like subjective effects. In the group who received ethanol, stress increased sedative-like effects and decreased stimulant-like effects. CONCLUSIONS: At this relatively high dose of ethanol, stress increased sedative effects of alcohol and did not increase desire for more alcohol. It is possible that in some individuals, the increased sedative effects after stress may increase the likelihood of consuming more alcohol. The effects of stress on consumption at this, or lower, doses of alcohol remain to be determined.