The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain

A low dose of the hallucinogen d-lysergic acid diethylamide (d-LSD) triggers a time- and region-dependent increase in c-Fos protein expression in specific rat forebrain areas. Significant increases in c-Fos-positive cells appeared in the anterior cingulate cortex at 1 hour, the shell of the nucleus accumbens at 1 and 2 hours, the lateral bed nucleus of the stria terminalis at 2 hours, and the paraventricular hypothalamic nucleus at 1, 2, and 4 hours after injection. This pattern suggests that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD.

Study at a glance

Abstract

The hallucinogen d-lysergic acid diethylamide (d-LSD) evokes dramatic somatic and psychological effects. In order to analyze the neural activation induced by this unique psychoactive drug, we tested the hypothesis that expression of the immediate-early gene product c-Fos is induced in specific regions of the rat forebrain by a relatively low, behaviorally active, dose of d-LSD (0.16 mg/kg, i.p.); c-Fos protein expression was assessed at 30 min, and 1, 2 and 4 h following d-LSD injection. A time- and region-dependent expression of c-Fos was observed with a significant increase (P<0.05) in the number of c-Fos-positive cells detected in the anterior cingulate cortex at 1 h, the shell of the nucleus accumbens at 1 and 2 h, the bed nucleus of stria terminalis lateral at 2 h and the paraventricular hypothalamic nucleus at 1, 2 and 4 h following systemic d-LSD administration. These data demonstrate a unique pattern of c-Fos expression in the rat forebrain following a relatively low dose of d-LSD and suggest that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD.