Skip to content
Research Article Open access CC BY 3.0

Morphine Treatment in Neonate Rats Increases Exploratory Activities: Reversal by Antagonist D2 Receptor

Joanna R. Rozisky, Gabriela Laste, Liciane F. Medeiros, Vinicius S. dos Santos, Lauren S. Adachi, Isabel C. de Macedo, Wolnei Caumo, Iraci L. S. Torres

Journal of Advances in Medicine and Medical Research · pp. 351–367 · Published 28 Sep 2013

10.9734/BJMMR/2014/3586

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.

Morphine open-field test elevated-plus-maze test exploratory-like behaviour D2 receptor neonate rat.

References (60)

  1. 1 The adolescent brain and age-related behavioral manifestations [DOI]
  2. 2 Drugs of abuse: anatomy, pharmacology and function of reward pathways [DOI]
  3. 3 Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies [DOI]
  4. 4 Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. [DOI]
  5. 5 Ethology and neurobiology of grooming behavior [DOI]
  6. 6 Psychobiology of novelty seeking and drug seeking behavior [DOI]
  7. 7 Periadolescence: Age‐dependent behavior and psychopharmacological responsivity in rats [DOI]
  8. 8 Animal models of ??anxiety??: where next? [DOI]
  9. 9 Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation. [DOI]
  10. 10 Ghrelin increases anxiety-like behavior and memory retention in rats [DOI]
  11. 11 Current Status of Pain Management in Children [DOI]
  12. 12 Enduring behavioral effects of early exposure to methylphenidate in rats [DOI]
  13. 13 Developmental differences in dopamine synthesis inhibition by (±)-7-OH-DPAT [DOI]
  14. 14 Time‐dose relationships for locomotor activity effects of morphine after acute or repeated treatment [DOI]
  15. 15 A sensitive open field measure of anxiolytic drug activity [DOI]
  16. 16 Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate–putamen in rats sensitized to morphine [DOI]
  17. 17 Postnatal development of multiple opioid receptors in rat brain [DOI]
  18. 18 Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation [DOI]
  19. 19 Morphine-induced long-term sensitization to the locomotor effects of morphine and amphetamine depends on the temporal pattern of the pretreatment regimen [DOI]
  20. 20 Postnatal development of multiple opioid receptors in the spinal cord and development of spinal morphine analgesia [DOI]
  21. 21 Normal inhibitory avoidance learning and anxiety, but increased locomotor activity in mice devoid of PrPC [DOI]
  22. 22 Interaction between isolation rearing and social development on exploratory behavior in male rats [DOI]
  23. 23 The neurobiology of infant pain: development of excitatory and inhibitory neurotransmission in the spinal dorsal horn [DOI]
  24. 24 Effects of morphine on rat behaviour in the elevated plus maze: The role of central amygdala dopamine receptors [DOI]
  25. 25 Early life experience alters behavioral responses to sweet food and accumbal dopamine metabolism [DOI]
  26. 26 The effect of neonatal handling on adult feeding behavior is not an anxiety‐like behavior [DOI]
  27. 27 Chronic and intermittent morphine treatment differently regulates opioid and dopamine systems: a role in locomotor sensitization [DOI]
  28. 28 Neonatal Morphine Administration Leads to Changes in Hippocampal BDNF Levels and Antioxidant Enzyme Activity in the Adult Life of Rats [DOI]
  29. 29 Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence [DOI]
  30. 30 Effects of dopamine D1 and D2 receptor antagonists on cocaine-induced place preference conditioning in preweanling rats [DOI]
  31. 31 Repeated subchronic exposure to phencyclidine elicits excessive atypical grooming in rats [DOI]
  32. 32 Increased elevated plus maze open-arm time in mice during spontaneous morphine withdrawal [DOI]
  33. 33 Dopamine–opioid interactions in the rat striatum: a modulatory role for dopamine D1 receptors in delta opioid receptor-mediated signal transduction [DOI]
  34. 34 Morphine exposure in early life increases nociceptive behavior in a rat formalin tonic pain model in adult life [DOI]
  35. 35 Long‐term effect of morphine administration in young rats on the analgesic opioid response in adult life [DOI]
  36. 36 Dopaminergic control of locomotion, mouthing, snout contact, and grooming: opposing roles of D1 and D2 receptors [DOI]
  37. 37 Modification of morphine sensitization by opioid and dopamine receptor antagonists: evaluation by studying ambulation in mice [DOI]
  38. 38 Memory expression is blocked by the infusion of CNQX into the hippocampus and/or the amygdala up to 20 days after training [DOI]
  39. 39 Perinatal methadone exposure and its influence on the behavioral ontogeny of rats [DOI]
  40. 40 Parametric and pharmacological analyses of the enhanced grooming response elicited by the D1 dopamine receptor agonist SKF 38393 in the rat [DOI]
  41. 41 Dopamine D-1 and D-2 receptor agonists and antagonists and neuropeptide-induced excessive grooming [DOI]
  42. 42 Ontogeny of behavioral sensitization in the rat: effects of direct and indirect dopamine agonists [DOI]
  43. 43 Fetal behavior and the dopamine system: Activity effects of D1 and D2 receptor manipulations [DOI]
  44. 44 Lifetime behavioural changes after exposure to anaesthetics in infant rats [DOI]
  45. 45 Changes to open field surfaces typically used to elicit hippocampal remapping elicit graded exploratory responses [DOI]
  46. 46 Effect of antenatal exposure to opiates on the development of opiate receptors in rat brain [DOI]
  47. 47 Fentanyl administration in infant rats produces long‐term behavioral responses [DOI]
  48. 48 Morphine treatment alters nucleotidase activities in rat blood serum [DOI]
  49. 49 Ontogeny of locomotor activity and grooming in the young rat: role of dopamine D1 and D2 receptors [DOI]
  50. 50 Reinforced responding of the 11-day-old rat pup: Synergistic interaction of D1 and D2 dopamine receptors [DOI]
  51. 51 Ethological and temporal analyses of anxiety-like behavior: The elevated plus-maze model 20 years on [DOI]
  52. 52 A psychomotor stimulant theory of addiction. [DOI]
  53. 53 Super-stereotypy I: Enhancement of a complex movement sequence by systemic dopamine D1 agonists [DOI]
  54. 54 ETHOLOGICALLY BASED ANIMAL MODELS OF ANXIETY DISORDERS [DOI]
  55. 55 Opioid systems and the newborn [DOI]
  56. 56 Neonatal morphine exposure alters E-NTPDase activity and gene expression pattern in spinal cord and cerebral cortex of rats [DOI]
  57. 57 Morphine treatment in early life alters glutamate uptake in the spinal synaptosomes of adult rats [DOI]
  58. 58 Ontogenetic determinants of behavioral responses to morphine in rats [DOI]
  59. 59 Behavioral and pharmacokinetic interaction between morphine and haloperidol in the rat.
  60. 60 [Differential contribution of dopamine D1 and D2 receptors in the mu-opioidergic immunomodulation].

Cited by 14

Morphine exposure during early life alters thermal and mechanical thresholds in rats

Ellen A. Nunes, Liciane Fernandes Medeiros, Joice Soares de Freitas · International Journal of Developmental Neuroscience · 2016

Long‐lasting behavioral and neurochemical effects of early‐life environmental enrichment in rats submitted to neonatal morphine administration

Matheus Gabriel de Freitas Nascimento, Josimar Macedo de Castro, Liciane Fernandes Medeiros · International Journal of Developmental Neuroscience · 2024

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect

Paulo Ricardo Marques Filho, Rafael Vercelino, Stefania Giotti Cioato · Progress in Neuro-Psychopharmacology and Biological Psychiatry · 2016

Neonatal morphine exposure and maternal deprivation alter nociceptive response and central biomarkers’ levels throughout the life of rats

Carla Oliveira, Roberta Ströher Toledo, Vanessa Leal Scarabelot · Neuroscience Letters · 2020

Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels

Carla de Oliveira, Vanessa L. Scarabelot, Rafael Vercelino · International Journal of Developmental Neuroscience · 2017

Showing 7 of 14 known citations — external sources report more than can currently be individually listed.

Article metrics

Real usage data collected on this platform.

10

Page views

0

PDF downloads

1

Outbound clicks

14

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.