Behavioral and electrophysiological evidence for opioid tolerance in adolescent rats.
Morphine and other opiates are successful treatments for pain, but their usefulness is limited by the development of tolerance. Given that recent studies have observed differential sensitivity to drugs of abuse in adolescents, the aim of this study was to assess antinociceptive tolerance to morphine in adolescent rats using both behavioral and cellular measures. Early (28-35 days postnatal) and late (50-59 days) adolescent and adult (73-75 days) male rats were injected with morphine (5 mg/kg, s.c.) or saline twice a day for two consecutive days. On Day 3, tolerance to morphine was evident in morphine-pretreated rats when tested on the hot plate test. Although baseline latencies for the early compared to late adolescent rats were faster, the magnitude of the shift in ED(50) for morphine was similar for the two adolescent groups. However, the shift in ED(50) tended to be greater in adolescent compared to adult rats. Subsequent to behavioral testing, whole cell patch-clamp recordings were made from ventrolateral PAG neurons. The opioid agonist, met-enkephalin (ME), activated similar outward currents in PAG neurons of early and late adolescent rats. However, reversal potentials of ME-induced currents were shifted to more hyperpolarized potentials in cells from morphine-pretreated rats. In addition, ME induced larger currents in morphine-pretreated rats with faster hot plate latencies compared to the mean (more tolerant) than in rats with slower latencies. These results indicate that repeated intermittent administration of morphine produces tolerance in adolescent rats that is associated with novel changes in opioid-sensitive ventrolateral PAG neurons.
Ingram
Susan L
SL
Department of Psychology, Washington State University Vancouver, Vancouver, WA 98686, USA. ingram@vancouver.wsu.edu
Fossum
Erin N
EN
Morgan
Michael M
MM
D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000528:radiation effects; D004361:Drug Tolerance; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine; D001418:Baclofen