Reduced serotonin synthesis during early embryogeny changes effect of subsequent prenatal stress on persistent pain in the formalin test in adult male and female rats.
The considerable evidence supporting a role for serotonin (5-HT) in the embryonic formation of CNS, mediation of prenatal stress, and pain processing is reviewed. Long-term influences of prenatal 5-HT depletion as well as its combination with prenatal stress effects on tonic nociceptive system in 90-day-old Wistar rats were studied in the formalin test. Pregnant dams were injected with para-chlorophenylalanine (pCPA, 400 mg/kg/2 ml, ip), producing 5-HT depletion during the early period of fetal serotonergic system development. The adult offspring from pCPA-treated dams revealed changes in behavioral indices of persistent pain (flexing + shaking and licking) in the formalin test (2.5%, 50 microl) that were accompanied by irreversible morphological alterations in the dorsal raphe nuclei. In the other series of experiments, the role of 5-HT in the mediation of prenatal stress on the behavioral indices of persistent pain was investigated in the adult offspring from dams with 5-HT depletion followed by restraint stress. Stress during the last embryonic week caused much more increase in flexing + shaking and licking in the second tonic phase of the response to formalin in offspring from pCPA- than saline-treated (control) dams. The former was characterized by alterations in the durations of the interphase, the second phase, and the whole behavioral response too. In offspring from pCPA-treated dams, sex dimorphism was revealed in tonic pain evaluated by licking. Together with our previous results in juvenile rats demonstrating the necessity of definite level of prenatal 5-HT for normal development of tonic nociceptive system, the present pioneering findings obtained in adult rats indicate that prenatal 5-HT depletion causes long-term morphological abnormalities in the dorsal raphe nuclei accompanied by alterations in behavioral indices of tonic pain. Early prenatal 5-HT depletion increases vulnerability of tonic nociceptive circuits to the following prenatal stress.
Butkevich
Irina Pavlovna
IP
Laboratory of Ontogenesis of Nervous System, IP Pavlov Institute of Physiology of the Russian Academy of Sciences, Nab. Makarova, 6. 199034, St. Petersburg, Russia. but@kolt.infran.ru
Mikhailenko
Victor Anatol'evich
VA
Vershinina
Elena Andreevna
EA
Khozhai
Ludmila Ivanovna
LI
Grigorev
Igor'Pavlovich
I
Otellin
Vladimir Alexandrovich
VA
D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D008297:Male; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis* / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*
D012701:Serotonin