Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation calls of rat pups.
Rat pups emit a highly stereotyped and well-characterized distress call in the ultrasonic range when socially isolated. We compared the modulatory influence of catecholamines and indoleamines on rat pup ultrasonic calls using pharmacologic probes. Administration of low doses of monoamine reuptake inhibitors produced significant, selective changes in the calls emitted by isolated 10-day-old pups. Acute administration of clomipramine (CMI; relatively 5-HT specific) reduced the rate of calling at low doses (1.0 and 5.0 mg/kg [3.2 and 18.0 mmol/kg] SC) but had reduced efficacy at higher doses (10 and 20 mg/kg [32.0 and 63.7 mmol/kg] SC). Motor activity and rectal body temperature were unaffected at these doses. Similarly, low doses of other 5-HT-selective uptake inhibitors, such as paroxetine (1.0 mg/kg [3.1 mmol/kg] SC) and citalopram (1.0 mg/kg [3.09 mmol/kg] SC), virtually eliminated isolation calling. The effects of CMI were not antagonized by either naltrexone (0.1 mg/kg [0.28 mmol/kg] SC) or Ro 15-1788 (5.0 mg/kg [16.5 mmol/kg] SC). Desipramine (DMI; norepinephrine [NE] specific) significantly increased calling rates at all doses tested (1.0 to 10.0 mg/kg [3.8 to 75 mmol/kg] SC). These effects were associated with significant reductions in body temperature, but not motor activity. Similar increases in the rate of isolation calling, reduction in rectal body temperature, and an increase in motor activity were produced by low doses of mazindol (0.5 mg/kg [1.75 mmol/kg] SC) and nortriptyline (1.0 mg/kg [19 mmol/kg] SC). In an additional study, the chronic effects of CMI and desipramine were evaluated with treatment beginning within 24 hours after birth.(ABSTRACT TRUNCATED AT 250 WORDS)
Winslow
J T
JT
Laboratory of Clinical Science, National Institute of Mental Health, NIHAC, Poolesville, MD 20837.
Insel
T R
TR
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002395:Catecholamines / Q000037:antagonists & inhibitors*; D015283:Citalopram / Q000494:pharmacology; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D008454:Mazindol / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000494:pharmacology; D009661:Nortriptyline / Q000494:pharmacology; D017374:Paroxetine; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013315:Stress, Psychological; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects*
D002395:Catecholamines; D010880:Piperidines; D012702:Serotonin Antagonists; D015283:Citalopram; D005442:Flumazenil; D017374:Paroxetine; D009271:Naltrexone; D009661:Nortriptyline; D008454:Mazindol; D002997:Clomipramine; D003891:Desipramine