ABSTRACT
Aims: The objective was to evaluate the single exposure of general anesthetics with or without a surgical procedure at postnatal day 14 (P14) on nociceptive behavioral responses. Furthermore, we evaluated ectonucleotidase activities at P14 and P30. Place of Study: All experiments were performed at the Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The Institutional Committee approved the experimental protocol f (GPPG-HCPA protocol No: 08149). Methodology: Fourteen-day-old male Wistar rats were divided into two experimental designs (ED): the 1st ED – control (C), isoflurane (ISO), isoflurane/surgery (ISO-SUR) and the 2nd ED – control (C), fentanyl/S(+)-ketamine (FK) and fentanyl/S(+)- ketamine/surgery (FK-SUR). Nociceptive responses were evaluated using the formalin and tail-flick tests, and the ectonucleotidase activities were evaluated by spinal cord synaptosome. All assessments were performed at P14 and P30. Results: The FK and FK-SUR groups displayed an increased latency at P30. For the ectonucleotidase activity analysis, the following results were observed: (a) in the 1st ED, the ISO group displayed a reduction in ATPase and ADPase, and both ISO and ISOSUR displayed a reduction in AMPase activity at P14; (b) in the 2nd ED, the FK group displayed an increase in AMPase activity at P14 and increased ATPase activity at P30, and both FK and FK-SUR exhibited an increase in AMPase activity at P30. Conclusion: Our results indicate that single administration of general anesthetics at P14 is able to promote changes in the nociceptive response in the intermediate-term, and in the ectonucleotidase activities in the short- and medium-terms.
ABSTRACT
Aims: Morphine treatment in early life is a practice widely used in paediatric intensive care units. However, the consequences of this treatment on behavioural responses throughout life have been poorly studied. It is well known that behavioural symptoms after morphine exposure are presumed to depend on certain changes in the dopaminergic system, and there is a strong evidence of the involvement of D2 receptor. In this way, our objective was to evaluate whether 5 μg morphine administration, once daily for 7 days in 8-day-old rats (P8), alters exploratory and anxiolitic-like behaviours over short- (P16) and medium-term (P30) periods in the open-field (OF) and elevated-plus maze (EPM) tests, and to verify the involvement of the D2 receptor in the behaviour changes. Place of Study: All experiments were performed at Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The experimental protocol was approved by the Institutional Committee for Animal Care and Use (GPPG-HCPA protocol No: 08345). Methodology: Wistar rats with 8-day-old (P8) received 5 μg of morphine administration, once daily for 7 days. The exploratory and anxiolitic-like behavious were analyzed in P16 and P30 by OF and EPM tests. At the ages where we observed significant differences in behaviour responses in both tests, the control and morphine groups were subdivided into three groups, each one designed to evaluate the effect of 0.2 mg/kg, 0.5 mg/kg or vehicle of i.p. administration of a dopamine D2 antagonist receptor (Haloperidol). Results: At short-term (P16) morphine group showed an increase in grooming, as well increase in exploratory behaviours at P30 in the OF test. In addition, anxiolytic-like behaviours were observed in the morphine group, such as increase of percentage of open arms behaviours and non-protected head dipping at medium-term in the EPM test. At the ages at which differences in behaviours were observed, both groups (control and morphine) received D2 antagonist receptor (haloperidol) 30 min before each test. All behaviours changes seen in the morphine group at P30 were totally reversed by haloperidol administration. Conclusion: Our findings demonstrate that morphine treatment in neonate period promotes behavioural changes in OF and EPM at P16 and P30. However, only alterations observed at P30 depend, at least in part, of dopaminergic system, particularly of the D2 receptor.