Developmental sources of variation in liability to adolescent substance use disorders.

This review provides a synthesis of the literature on the complex sequence of maturational, psychosocial, and neuroadaptive processes that lead to substance use disorders (SUD) in adolescence. A brief overview introduces the concepts of liability to SUD and epigenesis. A theory is presented explaining how affective, cognitive, and behavioral dysregulation in late childhood is exacerbated during early and middle adolescence by family and peer factors, as well as puberty, leading to substance use.

Time-dependent sensitization: the odyssey of a scientific heresy from the laboratory to the door of the clinic.

This review provides both a biological and clinical perspective on Time-Dependent Sensitization (TDS), an ancient amplified memory response to threat manifest in the ability of both drugs and nondrug stressors to induce neuronal and behavioral effects which strengthen entirely as a function of the passage of time following even a single or acute exposure. Evidence is presented to show that TDS may be involved in the development of a spectrum of diseases and how drug regimens based on the principles of TDS could provide a novel and revolutionary means of treating psychiatric and other illnesses.

Long-term oscillation of corticosterone following intermittent cocaine.

We have shown that repeated administration of cocaine, as well as other drugs and nondrug stressors, can induce alternating increases and decreases in several neurotransmitter and endocrine endpoints, which we call oscillation. Oscillation studies have typically used 3-4 pretreatments with cocaine or other agents, raising the question of whether oscillation lasts beyond this point. Using plasma corticosterone as our endpoint measure, we therefore inquired whether oscillation would persist across eight administrations of cocaine over a 28-day period.

Low CSF soluble interleukin 2 receptor levels in acute depression. Short communication.

Thirteen patients with DSM-III-R diagnosis of either major depression or bipolar I depression participated in the study. The control group consisted of 10 subjects evaluated for headache or suspected meningitis, none of whom were found to suffer from any organic disease. CSF was withdrawn from all subjects for the measurement of soluble interleukin 2 receptor (sIL-2R).

Cocaine-induced oscillation is conditionable.

We have recently shown that under some circumstances, sensitization produced by a stimulant such as cocaine (COC) can give way, with successive drug administrations, to alternating attenuations and reinstatements of the effect, an outcome that we have termed oscillation. Because sensitization to COC can be conditioned, we inquired whether COC-induced oscillation also was conditionable. The end point used was shock-induced hypoalgesia (paw withdrawal from a hot plate), as we have previously shown that oscillation follows initial sensitization of this measure with one to five pretreatments of 12 mg/kg (IP) of COC spaced at 1-week intervals, with the last COC injection occurring 30 min prior to the footshock.