Caffeine-Induced Psychosis and a Review of Statutory Approaches to Involuntary Intoxication.

Caffeine is the most commonly ingested psychoactive substance in the world. Although caffeine-use disorder is not recognized as a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, five disorders related to caffeine use are enumerated therein. An evolving literature suggests that caffeine is one of many licit substances that may cause psychotic symptoms in higher doses. Here, we present a case in which a defendant ingested large quantities of caffeine, which result in transient psychosis and a successful affirmative defense of involuntary intoxication. The purpose of this article is to summarize states' statutory approaches to involuntary intoxication, given that the term is defined variably, if defined at all. Evaluators must be careful to apply jurisdictionally appropriate standards in involuntary intoxication defenses because the bar for this total defense differs across localities.

Gonadal hormones modulate the potency of the disruptive effects of donepezil in male rats responding under a nonspatial operant learning and performance task.

In contrast to estrogen in female rats, testosterone in male rats may decrease cholinergic activity in the brain, thereby attenuating behaviors mediated by the cholinergic system. To investigate this possibility, the interactive effects of the gonadal hormones and donepezil, an acetylcholinesterase (AChE) inhibitor, on the responding of male rats were examined under a multiple schedule of repeated acquisition and performance of response sequences and on AChE activity in specific brain regions. Donepezil dose-effect curves (0.56-10 mg/kg) were determined in males that were gonadally intact, gonadectomized (GX), GX with testosterone replacement (GX+T) or GX with estradiol replacement (GX+E). In all four groups, donepezil produced dose-dependent rate-decreasing and error-increasing effects in the acquisition and performance components. However, disruptions of response rate and accuracy in both components occurred at lower doses in GX and GX+E males than in intact males. The GX+E males also had the highest percentage of errors under control (saline) conditions in the acquisition components. In terms of AChE activity, GX males had higher levels in the prefrontal cortex, striatum and hippocampus, but lower levels in the midbrain, compared with intact males; hypothalamic and cortical levels were comparable for the GX and intact groups. Together, these results in male rats indicate that the potency of donepezil's disruptive effects on the responding under a complex operant procedure requiring learning and performance of response sequences depends upon the gonadal hormone status, and that the effects of testosterone on cholinergic activity vary among brain regions.

Effects of selective serotonin2 ligands on behaviors evoked by stress in the rat.

Serotonin (5-HT) has been implicated in the regulation of the stress response. Two experiments were conducted to investigate the possibility that the 5-HT(2A), 2C agonist DOI would reduce behavioral responsiveness to stress, and that selective blockade of one or both of these receptor subtypes would reverse this effect. Stressors employed were mild tail pinch and an illuminated open field. In Experiment 1 DOI (0.1, 0.5, 1.0 mg/kg, s.c.) was found to decrease stress-evoked oral behavior directed at food and to increase rearing behavior in a dose-dependent fashion. Neither of these effects was reversed by spiperone (5-HT(2A) antagonist) or SDZ SER-082 (5-HT(2C) antagonist). DOI also increased the frequency of head shaking. This effect was reversed by SDZ SER-082. In Experiment 2 DOI was injected singly or in combination with ketanserin (5-HT(2A). 2C antagonist). DOI decreased tail pinch-evoked oral behavior directed at food, the amount of food eaten, and increased vocalization. In the open field DOI decreased rearing, increased the number of head shakes, and increased the incidence of flat body posture. While ketanserin alone (0.5, 2.5, 5.0 mg/kg) had no effect on any behavioral measure, coadministration of ketanserin (5.0 mg/kg) with DOI (0.5 and 1.0 mg/kg) significantly blocked the effects of DOI on oral behavior directed at food, eating, rearing, head shaking, and flat body posture. It is concluded that the observed effects of DOI on behaviors evoked by stress were mediated by activation of both 5-HT(2A) and 5-HT(2C) receptors.

Behavioral responses to stress following central and peripheral injection of the 5-HT(2) agonist DOI.

Evidence suggests that serotonin (5-HT) systems are involved in the regulation of an organism's response to stress. Experiments were conducted to evaluate the possibility that central (20, 100, or 200 microg icv), peripheral (0.1, 0.5, or 1.0 mg/kg sc), or combined central (200 microg) plus peripheral (0.1 mg/kg) injections of the selective 5-HT(2) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) would alter behavioral responses to stress in rats. Animals were evaluated during tail pinch stress, in an open field, and on a rotarod task. Across the three modes of administration (icv, sc, icv+sc), DOI resulted in a dose-related decrease in five of seven classes of behaviors observed during tail pinch. This reduction was most pronounced following subcutaneous injections, but occurred following intracerebroventricular and combined subcutaneous and intracerebroventricular injections as well. An additive effect of combined intracerebroventricular and subcutaneous administration was suggested by the fact that doses which were ineffective when given singly by these two routes resulted in a reduction in stress-evoked behavior when given together. Reduced responding seemed not to be attributable to general motoric impairment as DOI did not affect locomotion, grooming, or rotarod performance. The results suggest that activation of 5-HT(2) receptors produces an anxiolytic effect in rats subjected to acute tail pinch stress.