Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.

Abstract

RATIONALE:

The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs.

OBJECTIVES:

The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory.

METHODS:

Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared.

RESULTS:

Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats.

CONCLUSION:

These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.

• Authors: Hong-Zhen Pan, Hwei-Hsien Chen
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 191 Issue 1 Pg. 119-25 (Mar 2007) ISSN: 0033-3158 [Print] Germany
• PMID: 17096081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Central Nervous System Stimulants
• Phenethylamines
• Purinergic P1 Receptor Antagonists
• Receptors, Purinergic P1
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• Caffeine
• N(6)-cyclopentyladenosine
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Animals
• Animals, Newborn
• Anxiety (metabolism, prevention & control)
• Avoidance Learning (drug effects)
• Behavior, Animal (drug effects)
• Body Temperature Regulation (drug effects)
• Brain (drug effects, growth & development, metabolism)
• Caffeine (toxicity)
• Central Nervous System Stimulants (toxicity)
• Female
• Hot Temperature
• Hyperalgesia (chemically induced, metabolism, physiopathology)
• Male
• Memory (drug effects)
• Motor Activity (drug effects)
• Pain Measurement
• Pain Threshold (drug effects)
• Phenethylamines (pharmacology)
• Purinergic P1 Receptor Antagonists
• Rats
• Rats, Sprague-Dawley
• Receptors, Purinergic P1 (metabolism)
• Time Factors