Neurosteroids and behavior.

Neurosteroid production may be a mechanism to counteract the negative effects of stress and return organisms toward homeostasis. Stress induces an increase in neurosteroid production. Neurosteroids affect two of the most widely distributed neurotransmitter and receptor systems in the central nervous system (CNS): gamma-aminobutyric acid (GABA) and glutamate. This ability of this class of compounds to affect both the primary excitatory and the inhibitory systems in the CNS allows the modulation of a wide array of behaviors. For example, neurosteroids modulate anxiety, cognition, sleep, ingestion, aggression, and reinforcement. In general, neurosteroids that are positive modulators of N-methyl-D-aspartate receptors enhance cognitive performance and decrease appetite. Neurosteroids that are positive modulators of GABAA receptors decrease anxiety, increase feeding and sleeping, and exhibit a bimodal effect on aggression that may be secondary to effects on anxiety and cognition. Some data suggest that neurosteroids have reinforcing effects, which could affect their clinical utility. Drug discrimination studies are helping scientists to dissect more closely the receptor systems affected by neurosteroids at the behavioral level.