Serotonergic dorsal raphe neurons: changes in spontaneous neuronal activity and responsiveness to 5-MeODMT following long-term amphetamine administration.

In rats pretreated with a high dose of D-amphetamine for six days, serotonergic neurons in the dorsal raphe nucleus showed a trend toward increased spontaneous firing rate and reduced responsiveness to the autoreceptor agonist 5-MeODMT compared to controls. The most notable effect was a strong correlation between spontaneous activity and drug response: faster-firing cells required higher doses of 5-MeODMT to be inhibited. No such correlation appeared in control animals. These results suggest that repeated amphetamine administration alters serotonergic autoreceptor sensitivity in the dorsal raphe.

Study at a glance

Abstract

Single-unit activity, characteristic of serotonergic neurons, was recorded in the dorsal raphe nucleus of urethane-anesthetized rats pretreated twice daily with saline or with 10.0 mg/kg D-amphetamine for 6 days. Compared to controls, amphetamine-pretreated animals showed a trend toward increased spontaneous firing rate and decreased responsiveness to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a serotonergic autoreceptor agonist. The most pronounced effect of amphetamine pretreatment, however, was a highly significant correlation between spontaneous neuronal activity, measured as either firing rate or interspike interval, and the 5-MeODMT response. Faster firing cells required predictably higher doses of 5-MeODMT to produce an inhibition. No such relationship was observed in control animals. Taken together, these results suggest that repeated administration of relatively high doses of amphetamine produces complex changes in the dorsal raphe including a shift in the sensitivity of serotonergic autoreceptors.