The 5-HT(1A) receptor agonist 8-OH-DPAT reduces rats' accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT(1A) receptors.
BACKGROUND
Whilst several studies have investigated the role of serotonergic receptor subtypes in learning and memory, relatively few studies have examined their role in attentional processes.


OBJECTIVE
The present study investigated the role of pre- and postsynaptic 5-HT1A receptors on rats' attentional performance in the five-choice serial reaction time task (5-CSRT).


METHODS
Hungry rats were trained in the 5-CSRT task to detect brief (0.5 s) flashes of light presented randomly in one of five locations with a fixed intertrial interval of 5 s paced by the rat. We studied the effects of 8-OH-DPAT, a 5-HT1A receptor agonist, at various subcutaneous (SC) doses (10-100 microg/kg) on measures of rats' discriminative accuracy (the index of attentional functioning) and various behavioural indices of response control and motivation. Manipulations of basic task parameters, intracerebroventricular (ICV) injections of 5,7-dihydroxytryptamine (5,7-DHT) to deplete forebrain 5-HT and treatments with a selective 5-HT1A receptor antagonist WAY 100635 were made in order to determine the behavioural and neural specificity of the effects of 8-OH-DPAT.


RESULTS
A dose of 100 microg/kg, but not lower doses, significantly reduced choice accuracy and increased errors of omission, latencies to respond correctly and to collect food reward and premature responses. All these effects were completely blocked by WAY 100635, injected SC 5 min before 8-OH-DPAT at doses from 10-100 microg/kg. WAY 100635 by itself had no effect in the task. Dimming the visual stimuli to one-third of the usual brightness did not modify the effect of 8-OH-DPAT on choice accuracy. Prolonging the stimuli from 0.5 to 1.0 s reversed 8-OH-DPAT's effect on choice accuracy but did not modify the other effects on rats' performance. An ICV injection of 150 microg 5,7-DHT, which depleted forebrain serotonin by 90%, reversed 8-OH-DPAT's effect on choice accuracy but did not modify the effects on errors of omission and latency to make correct responses. Similar effects were found by infusing 1.0 microg/0.5 microl WAY 100635 in the dorsal raphe 5 min before 8-OH-DPAT. 8-OH-DPAT increased the latency to collect the reinforcement; this effect was attenuated by ICV 5,7-DHT and completely antagonized by WAY 100635 in the dorsal raphe. Rats treated with 5,7-DHT or 8-OH-DPAT showed more premature responses and these effects were markedly reduced by the combined treatment.


CONCLUSIONS
The results suggest that stimulation of presynaptic 5-HT1A receptors is involved in the ability of 8-OH-DPAT to cause attentional dysfunction and enhance impulsivity while slowing of responding and increase in errors of omission mainly depend on stimulation of post-synaptic 5-HT1A receptors.
Carli
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Samanin
R
R
D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D007175:Impulsive Behavior; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D016548:Prosencephalon / Q000293:injuries; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin