Abstract
A modulatory role for serotonin has been described for the development and expression of the ultransonic call of infant rat pups during brief maternal separations. In previous studies, serotonin reuptake inhibitors selectively reduced the rate of calling following acute administration to 9–11-day-old pups and a serotonin neurotoxin (MDMA) systematically disrupted the development of ultrasonic vocalizations but not other measures of motor development. In the current studies, we extended our investigations to include drugs with purported receptor subtype selectivities. Consistent with previous reports, acute administration of 5HT1A agonists buspirone and 8-OH-DPAT ((±)-8-hydroxy-2-(di-N-propylamino)tetralin) reduced the rate of calling at doses which did not affect motor activity or core body temperature. The rate reducing effects of buspirone persisted up to 1 but not 2 h after injection. Administration of purported 5HT1B receptor agonists, CGS12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a] quinoxaline) and TFMPP (1-[3-fluoromethyl)phenyl]-piperazine) increased the rate of calling depending on the specificity of the drug for the 5HT1B receptor.d,l-Propranolol, a 5HT1 receptor antagonist, blocked the effects of both 8-OH-DPAT and TFMPP. m-CPP (1-(3-chlorophenyl)piperazine) and DOI ((±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), drugs with putative actions at 5HT1C and 5HT2 receptor sites both decreased calling but differed according to their effects on motor activity. Ritanserin, a 5HT2 and 5HT1C antagonist, produced a dose-related increase in call rate. A dose of ritanserin with no apparent intrinsic effects effectively antagonized DOI rate reducing effects but potentiated the rate reducing effects of m-CPP. These data extend previous studies demonstrating a role for serotonin in the expression of rat pup separation calls and further demonstrate that 5HT may increase or decrease calling depending on with receptor subtype is affected.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Benjamin D, Lal H, Meyerson LR (1990) The effects of 5HT1B characterizing agents in the mouse elevated plus-maze. Life Sci 47:195–203
Berendsen HH, Broekkamp CL (1987) Drug-induced penile erections in rats: indications of serotonin receptor mediation. Eur J Pharmacol 135:279–287
Broekemp C, Jenk F (1989) The relationship between various animal models of anxiety, fear-related psychiatric syndromes and response to serotonergic drugs. In: Bevan P, Cools A, Archer T (eds) Behavioural pharmacology of 5H-T. Lawrence Erlbaum, Hillsdale, NJ, pp 321–337
Burkholder JH, Hill JL, Vaughn WJ, Casio HE (1982) A broad-band digitizing rat detector: simultaneous recording from all sound frequencies in the range of rat ultrasonic vocalizations. Behav Res Meth Instr 14:511–518
Ceulemans DLS, Hoppenbrouwers M, Gelders YG, Reyntjens AJM (1985) The influence of ritanserin, a serotonin antagonist, in anxiety disorders. A double-blind placebo-controlled study versus lorazepam. Pharmacopsychiatry 18:303–305
Curzon G, Kennett GA (1990) mCPP: a tool for studying behavioural responses associated with 5-HT1C receptors. TIPS 11:181–182
Engel G, Gother M, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Arch Pharmacol 332:1–7
Enters EK, Spears LP (1988) Ontogenetic transitions in the psychopharmacological response to serotonergic manipulations. Psychopharmacology 96:161–168
Erikkson E, Humble M (1990) Serotonin in psychiatric pathophysiology: a review of data from experimental and clinical research. In: Pohl R, Gershon S (eds) The biological basis of psychiatric treatment. Progress in basic and clinical pharmacology. Karger, Basel, pp 66–119
Gardner CR (1985) Inhibition of ultrasonic distress vocalizations in rat pups by chlordiazepoxide and diazepam. Drug Dev Res 5:185–193
Gardner CR, Buddhram P (1987) Effects of agents which interact with central benzodiazepine binding sites on stress. Eur J Pharmacol 134:275–283
Goodwin GM, De Souza RJ, Green AR, Heal DJ (1987) The pharmacology of the behavioral and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Psychopharmacology 91:506–511
Hamik A, Peroutka SJ (1989) 1-(m-Chlorophenyl)piperazine (mCPP interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 25:569–575
Hamon M, Lanfumey L, El Mestikawy S, Boni C, Miquel M-C, Bolanos F, Schecter L, Gozlan H (1990) The main features of central 5-HT receptors. Neuropsychopharmacology 3:349–360
Hård E, Engel J (1988) Effects of 8-OH-DPAT on ultrasonic vocalization and audiogenic immobility reaction in pre-weaning rats. Neuropharmacology 27:981–986
Hård E, Engel J, Lindh A-S (1988) Effect of clonidine on ultrasonic vocalization in preweaning rats. J Neural Transm 73:217–237
Hartig PR, Hoffman BJ, Kaufman MJ, Hirata F (1990) The 5-HT1C receptor. In: Whitaker-Azmitia PM, Peroutka SJ (eds) The neuropharmacology of serotonin. The New York Academy of Sciences, New York, pp 149–167
Hofer MA, Shair HN (1987) Isolation distress in two-week-old rats: influence of home cage, social companions, and prior experience with littermates. Dev Psychobiol 20:465–476
Hofer MA, Shair HN, Murowchick E (1989) Isolation distress and maternal comfort responses of two-week-old rat pups reared in social isolation. Dev Psychobiol 22:553–556
Hutson PH, Kennett GA, Donohoe TP, Dourish CT, Curzon G (1989) Opposite effects of 5HT1A and 5HT1B/1C agonists on food intake. In: Bevan I, Cools AR, Archer T (eds) Behavioral pharmacology of 5-HT. Lawrence Erlbaum, Hillsdale, NJ, pp 283–287
Insel T, Winslow J (1990) Neurobiology of obsessive-compulsive disorder: a possible role for serotonin. J Clin Psychiatry 51:1–9
Insel TR, Winslow JT (1991) Rat pup ultrasonic vocalizations: an ethologically relevant behavior responsive to anxiolytics. In: Olivier B, Mos J (eds) New animal models of psychiatric illness (in press)
Insel TR, Hill JL, Mayor RB (1986) Rat pup ultrasonic isolation calls: possible mediation by the benzodiazepine receptor complex. Pharmacol Biochem Behav 24:1263–1267
Insel TR, Miller LP, Gelhard RE, Hill JL (1988) Rat pup ultrasonic isolation cells and the benzodiazepine receptor. In: Newman JD (ed) The physiological control of mammalian vocalization. Plenum Press, New York, pp 331–342
Kehoe P (1988) Ontogeny of adrenergic and opioid effects on separation vocalizations in rats. In: Newman J (ed) The physiological control of mammalian vocalization. Plenum Press, New York, pp 301–320
Kehoe P, Blass EM (1986) Opioid-mediation of separation distress in 10-day-old rats: reversal of stress with maternal stimuli. Dev Psychobiol 19:385–398
Kennett G, Whitton P, Shah K, Curzon G (1989) Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists. Eur J Pharmacol 164:445–454
Middlemiss DN, Hutson PH (1990) The 5-HT1B receptors. In: Whitaker-Azmitia PM, Peroutka SJ (eds) The neuropharmacology of serotonin. The New York Academy of Sciences, New York, pp 132–149
Morin D, Hennequin S, Monteau R, Hilaire G (1990) Serotonergic influences on central respiratory activity: an in vitro study in the newborn rat. Brain Res 535:281–287
Mos J, Olivier B (1989) Ultrasonic vocalizations by rat pups as an animal model for anxiolytic activity: effects of serotonergic drugs. In: Archer T, Bevan PAC (eds) Behavioural pharmacology of 5-HT. Lawrence Erlbaum, Hillsdale, NJ, pp 361–366
Neale RF, Fallon SL, Boyar WC, Wasley JWF, Martin LL, Stone GA, Glaeser BS, Sinton CM, Williams M (1987) Biochemical and pharmacological characterization of CGS12066B, a selective serotonin-1B agonist. Eur J Pharmacol 136:1–9
Noirot E (1966) Ultra-sounds in young rodents. I. Changes with age in albino mice. Anim Behav 14:459–462
Noirot E (1972) Ultrasounds and maternal behavior in small rodents. Dev Psychobiology 5:5–21
Renyi L, Lewander T (1989) 5-HT1A and 5-HT1B agonists produce opposite effects on the ejaculatory response induced by amphetamine in rats. In: Bevan I, Cools AR, Archer T (eds) Behavioral pharmacology of 5-HT. Lawrence Erlbaum, Hillsdale, NJ, pp 79–83
Shannon M, Battaglia G, Glennon RA, Titeler M (1984) 5HT1 and 5HT2 binding properties of derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA). Eur J Pharmacol 102:23–29
Smotherman WP, Bell RW, Starzec I, Ellias J, Zachman TA (1974) Maternal responses to infant vocalizations and olfactory cues in rats and mice. Behav Biol 12:55–66
Soubrie P (1986) Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 9:319–364
Taylor DP (1987) Buspirone, a new approach to the treatment of anxiety. FASEB 2:2445–2552
Titeler M, Lyon RA, Davis KH, Glennon RA (1987) Selectivity of serotonergic drugs for multiple brain serotonin receptor: the role of3H-DOB, a 5-HT2 agonist radioligand. Biochem Pharmacol 36:3265–3271
Titeler M, Lyon RA, Glennon RA (1988) Radioligand binding evidence implicates the brain 5-HT2 receptor as the site-of-action for LSD and phenylisoproylamine hallucinogens. Psychopharmacology 94:213–216
Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New York
Winslow JT, Insel TR (1990a) Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation call of rat pups. Neuropsychopharmacology 3:51–59
Winslow JT, Insel TR (1990b) Serotonergic modulation of rat pup ultrasonic vocal development: studies with MDMA. J Pharmacol Exp Ther 254:212–220
Winslow JT, Insel TR (1991) Endogenous opioid's: do they mediate the rat pup's response to social isolation? Behav Neurosci 105:31–41
Winslow JT, Insel TR, Trullas R, Skolnick P (1990) Rat pup isolation calls are reduced by functional antagonists of the NMDA receptor complex. Eur J Pharmacol 190:11–21
Wozniak KM, Aulakh CS, Hill JL, Murphy DL (1988) The effect of 8-OH-DPAT on temperature in the rat and its modification by chronic antidepressant treatments. Pharmacol Biochem Behav 301:451–456
Wozniak KM, Aulakh CS, Hill JL, Murphy DL (1989) Hyperthermia induced by m-CPP in the rat and its modification by anti-depressant treatments. Psychopharmacology 97:269–274
Zohar J, Muellar EA, Insel TR, Zohar-Kadouch RC, Murphy DL (1987) Serotonergic responsivity in obsessive-compulsive disorder: comparison of patients and healthy controls. Arch Gen Psychiatry 44:946–951
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Winslow, J.T., Insel, T.R. Serotonergic modulation of the rat pup ultrasonic isolation call: studies with 5HT1 and 5HT2 subtype-selective agonists and antagonists. Psychopharmacology 105, 513–520 (1991). https://doi.org/10.1007/BF02244372
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244372