lithium-chloride and 4-iodo-2-5-dimethoxyphenylisopropylamine

The effects of chronic lithium administration on regional brain incorporation coefficients k* of arachidonic acid (AA), a marker of phospholipase A2 (PLA2) activation, were determined in unanesthetized rats administered i.p. saline or 1 mg/kg i.p. (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a 5-HT2A/2C receptor agonist. After injecting [1-(14)C]AA intravenously, k* (brain radioactivity/integrated plasma radioactivity) was measured in each of 94 brain regions by quantitative autoradiography. Studies were performed in rats fed a LiCl or a control diet for 6 weeks. In the control diet rats, DOI significantly increased k* in widespread brain areas containing 5-HT2A/2C receptors. In the LiCl-fed rats, the significant positive k* response to DOI did not differ from that in control diet rats in most brain regions, except in auditory and visual areas, where the response was absent. LiCl did not change the head turning response to DOI seen in control rats. In summary, LiCl feeding blocked PLA2-mediated signal involving AA in response to DOI in visual and auditory regions, but not generally elsewhere. These selective effects may be related to lithium's therapeutic efficacy in patients with bipolar disorder, particularly its ability to ameliorate hallucinations in that disease.

Topics: Amphetamines; Animals; Arachidonic Acid; Brain; Lithium Chloride; Male; Rats; Rats, Inbred F344; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Serotonin Receptor Agonists; Signal Transduction

Electrical stimulation of the dorsal raphe nucleus of Sprague-Dawley rats was used as the cue for discrimination using a taste aversion paradigm. Rats were trained to associate saccharin drinking during electrical stimulation of the dorsal raphe nucleus with LiCl injection after the session as the aversive unconditioned stimulus. In sessions without stimulation, rats were allowed to consume saccharin and received a saline injection after the session. Suppression of saccharin consumption during electrical stimulation was learned within 12 trials. Rats trained in the reverse discrimination, i.e., sessions with no electrical stimulation paired with LiCl injection, showed a similar learning curve. Animals injected prior to the session with the hallucinogenic 5-HT2 agonist (+/-)-DOI associated DOI with electrical stimulation of the dorsal raphe nucleus. Thus, animals may be trained to discriminate electrical stimulation of the dorsal raphe nucleus. Furthermore, animals generalize from activation of 5-HT2 receptors to electrical stimulation of the dorsal raphe nucleus.

Topics: Amphetamines; Animals; Cues; Discrimination Learning; Electric Stimulation; Generalization, Stimulus; Lithium Chloride; Male; Raphe Nuclei; Rats; Rats, Sprague-Dawley; Serotonin Receptor Agonists; Taste