5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned and unconditioned fear in rats.
BACKGROUND
It is well known that 5-HT(2) mechanisms modulate the defensive behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety, only studies with the stimulation of the dPAG of rats without previous aversive experience have been conducted so far.


OBJECTIVE
We investigated the mediation of 5-HT(2) receptors of the dPAG in rats previously submitted to contextual fear conditioning (CFC). Defensive behaviors induced by the activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during the testing sessions of CFC in which animals were placed in a context previously paired to footshocks. The 5-HT(2) function of the dPAG in this condition was evaluated by local injections of alpha-methyl-5-HT (20 nmol/0.2 mul) and ketanserin (5 and 10 nmol/0.2 mul), selective agonist and antagonist of 5-HT(2) receptors, respectively.


RESULTS
In accordance with previous studies, alpha-methyl-5-HT increased the aversive thresholds (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG did not produce significant effects. On the other hand, ketanserin decreased in a dose-dependent manner the freezing threshold (proaversive effect) determined by the dPAG electrical stimulation, whereas alpha-methyl-5-HT continued to show antiaversive effects in animals under CFC.


CONCLUSIONS
The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT(2) receptors within the dPAG with important impact on the expression of defensive behaviors.
Oliveira
Luciana Chrystine
LC
Instituto de Neurociencias & Comportamento, Campus USP, 14040-901, Ribeirão Preto, Sao Paulo, Brazil.
Broiz
Ana Carolina
AC
de Macedo
Carlos Eduardo
CE
Landeira-Fernandez
J
J
Brandão
Marcus Lira
ML
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004924:Escape Reaction / Q000502:physiology; D005239:Fear / Q000523:psychology; D046352:Freezing Reaction, Cataleptic; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D010487:Periaqueductal Gray / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D007650:Ketanserin