Serotonergic dorsal raphe neurons: changes in spontaneous neuronal activity and responsiveness to 5-MeODMT following long-term amphetamine administration.
Neuroscience letters August 14, 1989 DOI: 10.1016/0304-3940(89)90489-8
Summary
Repeated administration of 10.0 mg/kg D-amphetamine in rats led to a notable increase in spontaneous firing rates of serotonergic neurons, with a significant correlation between neuronal activity and response to the serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Specifically, faster-firing neurons required higher doses of 5-MeODMT to inhibit activity, a relationship absent in control animals. This research involved 24 urethane-anesthetized rats and indicates that high doses of amphetamine can significantly alter serotonergic autoreceptor sensitivity in the dorsal raphe nucleus.
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.