Lack of evidence for context-dependent cocaine-induced sensitization in humans: preliminary studies.

Cocaine-induced behavioral sensitization is the well-documented phenomenon where repeated doses of cocaine elicit increasingly greater effects on motoric activity in rats. Some observations suggest that behavioral sensitization may provide a model for understanding the mechanisms of drug-craving elicited by environmental triggers or cues. The process of fully validating such an animal model for its ability to detect effective anticraving medicines is a difficult and long-term undertaking. As a first step in that direction, we decided to determine if cocaine can produce conditioned behavioral sensitization in humans using a paradigm fairly similar to that used for rodents. Because humans do not react to cocaine with the pronounced motor activation observed in rodents, we measured a variety of end points, including blood pressure (BP), heart rate (HR), respiratory rate, pupil diameter, hormones (prolactin and cortisol), and subjective responses using the questionnaire for drug-related feelings (QDRF) and the EEG. To mimic the home and test cages used in rodent studies, two rooms were used: a small test chamber and a regular room with a window and furnishings. On day 1 each subject received a drug infusion (either saline or 40 mg cocaine IV) in both locations. On day 2, all subjects received an infusion (saline or 25 mg cocaine IV) in the test chamber. All drug infusions were conducted double blind. The paired group received cocaine on both days in the test chamber. The unpaired group received cocaine in regular room on day 1, and cocaine in the test chamber on day 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine-induced increases in EEG alpha and beta activity: evidence for reduced cortical processing.

To understand the effects of cocaine on the cerebral cortex, 14 male polydrug abusers were enrolled in a study on the effects of cocaine on the electroencephalogram (EEG). The experimental treatments were placebo, 20 mg cocaine or 40 mg cocaine i.v. administered in a double-blind, pseudorandom design. The EEG was recorded from 13 electrode positions over the left hemisphere during a 3-minute baseline recording and for 30 minutes after initiation of the i.v. injection. The spectral power for delta, theta, alpha and beta EEG bands was calculated from data collected in each 3-minute interval. Cocaine significantly increased beta in frontal and central areas and enhanced alpha in frontal and temporal regions. Cocaine-induced increases in EEG beta power had a cortical distribution similar to those produced by barbiturates and benzodiazepines. As all of these drugs reduce cortical glucose metabolism, the increases in beta power may reflect a reduction in cortical neural activity.

Dose-dependent atropine-induced changes in spontaneous electroencephalogram in human volunteers.

Atropine is an anticholinergic drug used in military medicine as an antidote following exposure to cholinesterase-inhibiting nerve agents. However, atropine causes neuropsychologic effects that impair performance. In the present study, we examined electrophysiologic indices that may accompany performance deficits. Quantitative electroencephalographic (EEG) analyses of changes induced by atropine (1.5, 3.0, and 6.0 mg/70 kg, intramuscularly) were assessed in seven male volunteers in a placebo-controlled, double-blind, cross-over experiment. Spontaneous EEG recordings were obtained from relaxed subjects before, 2 hours after, and 8 hours after atropine. Atropine significantly increased delta power, decreased alpha power, and tended to increase theta power and reduce beta and theta frequency. EEG indices of vigilance were reduced by the drug. Dose-related increases in sedation and dysphoria were obtained; some subjects liked these effects. Together, these findings confirmed that atropine causes dose- and time-related electrophysiologic and subjective effects that predict impaired performance.