Isolated preweanling rats emit ultrasonic vocalizations. Mu- and delta
-opioid agonists quiet isolated pups; naltrexone, an opioid receptor b
locker, prevents this quieting. A littermate companion is as effective
as morphine in quieting vocalizations, and naltrexone also blocks com
panion quieting. We have now quantified methionine enkephalin (Met-ENK
) immunoreactivity in the brains of 10-day-old Wistar rat pups taken d
irectly from the home cage or kept either alone or with a companion fo
r a brief or prolonged period. Met-ENK is an endogenous ligand that bi
nds to the mu- and delta-opioid receptors. Striatal peptide levels wer
e higher when pups were with a companion than when they were kept alon
e; the peptide level of pups in the home cage did not differ from eith
er. Comparisons of pups in the brief (5 min) and prolonged (60 min) se
paration conditions showed significantly higher peptide levels followi
ng a brief period out of the nest than at the end of an hour. In hypot
halamus, hippocampus, and frontal cortex neither social condition nor
duration of separation significantly altered peptide quantity. Larger
amounts of Met-ENK in pups provided with a companion could reflect an
increase in posttranslational cleavage of the precursor molecule leadi
ng to stimulation of receptors that act to diminish USV. Reduced level
s following 60 min out of the home cage might reflect depletion of the
peptide following an initial release during the period when the pup's
vocal response is most vociferous.