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T R Insel

Publications and source records attributed to T R Insel.

At least 19 recordsLinked to original sources
PubMed1992

Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles.

The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor expression in brain. By in vitro receptor autoradiography with an iodinated oxytocin analogue, specific binding to brain oxytocin receptors was observed in both the monogamous prairie vole (Microtus ochrogaster) and the polygamous montane vole (Microtus montanus). In the prairie vole, oxytocin receptor density was highest in the prelimbic cortex, bed nucleus of the stria terminalis, nucleus accumbens, midline nuclei of the thalamus, and the lateral aspects of the amygdala. These brain areas showed little binding in the montane vole, in which oxytocin receptors were localized to the lateral septum, ventromedial nucleus of the hypothalamus, and cortical nucleus of the amygdala. Similar differences in brain oxytocin receptor distribution were observed in two additional species, the monogamous pine vole (Microtus pinetorum) and the polygamous meadow vole (Microtus pennsylvanicus). Receptor distributions for two other neurotransmitter systems implicated in the mediation of social behavior, benzodiazepines, and mu opioids did not show comparable species differences. Furthermore, in the montane vole, which shows little affiliative behavior except during the postpartum period, brain oxytocin receptor distribution changed within 24 hr of parturition, concurrent with the onset of maternal behavior. We suggest that variable expression of the oxytocin receptor in brain may be an important mechanism in evolution of species-typical differences in social bonding and affiliative behavior.

Animals↗
PubMed1992

Oxytocin and social bonding.

The prairie vole is an excellent model for examining the neurobiology of social attachment, and in particular of pair-bond formation. In female prairie voles either sexual interactions or oxytocin infusions can hasten the formation of a partner preference. These results implicate oxytocin in the formation of adult heterosexual social bonds. In conjunction with work on other social systems described in this volume, these findings also support the suggestions of Klopfer and Newton that oxytocin may be important in coordinating mammalian social interactions with other critical reproductive events such as birth, lactation, and sexual behavior.

Aggression↗
PubMed1992

Effects of chlordiazepoxide and beta-carboline 3-carboxylic acid ethyl ester on non-suppressed and minimally-suppressed responding in the squirrel monkey.

Lever-pressing of squirrel monkeys was maintained under a multiple fixed-interval (FI) 5-min schedule of food presentation. In one component, responding was suppressed to various degrees by the presentation of electric shock following each 30th response. When responding was either substantially or minimally suppressed, intermediate doses of chlordiazepoxide (CDAP, 1-30 mg/kg) increased both suppressed and non-suppressed responding. Beta-carboline 3-carboxylic acid ethyl ester (beta-CCE, 0.1-3 mg/kg) had little effect at low to intermediate doses (0.1-0.3 mg/kg) and decreased both minimally-suppressed and non-suppressed responding to a comparable extent at higher doses. Repeated daily dosing with beta-CCE (up to 10 mg/kg) resulted in rapid tolerance to its rate-decreasing effects. As agonists do not typically exhibit rapid tolerance for anxiolytic efficacy, the current results suggest that some behavioral effects of inverse agonists may not be strictly opposite those of benzodiazepines.

Animals↗
PubMed1992

Enhanced social interactions in rats following chronic, centrally infused oxytocin.

Most studies investigating the behavioral effects of centrally administered oxytocin (OT) have been confined to single acute injections followed by brief behavioral observations lasting up to 90 min. The present study examines the behavioral effects of chronic, centrally administered OT in male rats observed continuously for prolonged periods of time. Either artificial cerebrospinal fluid or OT was centrally infused (via osmotic minipump) to gonadally intact male rats. Behavioral observations were made on males paired with either ovariectomized or estrous females during a 6-h time period. Most striking was the observation that durations of physical contact were doubled in pairs containing OT-infused males, even in the absence of sexual interactions. Also, OT-infused males showed significantly higher levels of anogenital sniffing of females and autogrooming; however, sexual interactions were unaffected by chronic OT. Chronic OT had no effect on body temperature, analgesia, or exploratory behavior in an open field. These findings suggest that chronic OT in male rats has behavioral effects that may significantly enhance adult social (nonsexual) interactions, possibly through alterations in olfactory and somatosensory information processing.

Analgesia↗
PubMed1992

Oxytocin--a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies.

Oxytocin (OT) is a nine amino acid peptide synthesized in hypothalamic cells which project either to the neurohypophysis or to sites within the central nervous system. Although neurohypophyseal OT release has long been associated with uterine contraction and milk ejection, the function of intracerebral OT remains unclear. On the basis of behavioral, cellular, and comparative studies, this review suggests that brain OT influences the formation of social bonds. The first part of this review examines evidence linking central OT to several forms of affiliation. Central administration of OT induces maternal and reproductive behaviors in rats primed with gonadal steroids. OT antagonists and hypothalamic lesions block the initiation of maternal and reproductive behaviors but have no effects on these behaviors once established. Our new studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact. These studies of parental, reproductive, and attachment behaviors suggest that exogenous OT has "prosocial" effects and that endogenous OT may be essential for initiating social interaction. In a second series of experiments, we investigated the cellular mechanisms for OT's effects on social behavior by means of autoradiographic receptor binding. In the rat forebrain, OT receptors are expressed in several limbic regions believed to be involved in the integration of sensory processing. The regulation of these receptors is surprisingly resistant to either ablation of OT cells or repeated central administration of OT. However, receptors in two regions, the bed nucleus of the stria terminalis (BNST) and the ventromedial nucleus of the hypothalamus (VMN), appear selectively induced by exogenous or endogenous increases in gonadal steroids. At parturition, binding to OT receptors increases 84% in the BNST, and at estrus, binding increases 35% in the VMN. These results demonstrate that physiologic changes in gonadal steroids can alter receptor expression in anatomically discrete target fields and thereby direct responsiveness to endogenous neuropeptide release. A model for OT's effects on social behavior is proposed, which relies on the heterologous regulation of the brain OT receptor. A third series of experiments tested the hypothesis that brain OT influences affiliation by comparing prairie and montane voles, two closely related species with dichotomous systems of social organization. Although no differences appear in the presynaptic expression of the neuropeptide, OT receptors are distributed in complementary patterns in the two species. In the highly affiliative prairie vole, receptors are most evident in the BNST and one of its primary afferents, the lateral amygdala, highlighting a circuit previously implicated in maternal behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Homologous regulation of brain oxytocin receptors.

Specific receptors for oxytocin have been identified in rat forebrain. Previous studies have demonstrated that in select regions, these receptors are dependent on heterologous induction by gonadal steroids. To investigate whether brain oxytocin receptors are homologously regulated by oxytocin, we measured oxytocin receptor binding after hypothalamic paraventricular nucleus lesions, repeated central injections of oxytocin, and continuous central infusion of oxytocin via osmotic minipump. Neither lesions of the paraventricular nucleus nor repeated oxytocin injections altered the binding of the selective oxytocin receptor ligand [125I]OTA [125I] d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin, as measured by in vitro receptor autoradiography. After 10 days of continuous oxytocin infusion by osmotic minipump, oxytocin receptor binding decreased in every target field by at least 50%. This decrease appeared to represent a down-regulation of receptors and not displacement by exogenous peptide, as it persisted for at least 24 h after pump removal, and binding remained reduced in the presence of a saturating concentration of [125I] OTA. Reduction of oxytocin receptors in response to increased oxytocin release may represent an important physiological mechanism for the regulation of central oxytocin neurotransmission.

Animals↗
PubMed1992

Neurobiology of obsessive compulsive disorder.

In this brief review of two of the neurobiologic aspects of OCD, two simplistic models have been suggested. Although these models reflect different perspectives, they may not be independent. For instance, the striatum, which is a focus for the neuroanatomic model, receives a dense serotonergic projection from the dorsal raphé. Similarly, as mentioned previously, combining PET studies and drug treatment demonstrates that the increased metabolic activity seen in the orbital cortex appears to normalize with serotonin uptake inhibitor treatment. Insights into the neurobiology of this syndrome will require combining perspectives as well as developing additional approaches. In addition, the search for neurobiologic abnormalities must be guided by a continuing regard for phenomenology. There is no reason, a priori, to assume that this syndrome subsumes only one disorder. The careful dissection of subgroups--whether based on symptom type, character style, or comorbid diagnoses--will be increasingly vital for understanding the results of neuropharmacologic and functional imaging studies.

Brain↗
PubMed1991

Central administration of oxytocin modulates the infant rat's response to social isolation.

Several lines of evidence suggest that oxytocin modulates the formation and maintenance of social bonds. In the current experiments we investigated the influence of centrally and peripherally administered oxytocin on the behavior of 6-8 day old rat pups during brief periods of social isolation. Ultrasonic vocalizations emitted by isolated pups were decreased following i.c.v. administration of oxytocin, at doses (500, 1000 ng) which did not affect motor activity. S.c. administered oxytocin (1, 10 micrograms) produced a biphasic change in ultrasonic vocalizations, depending on dose. Central administration of the oxytocin antagonist (d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH2(9)]OVT) (OTA, 500 ng) did not measurably affect pup behavior by itself but did block the decrease in calls following central but not peripheral administration of oxytocin. These data demonstrate that oxytocin via its central receptor can regulate the response to social isolation.

Angiotensin Receptor Antagonists↗
PubMed1991

Vasopressin modulates male squirrel monkeys' behavior during social separation.

The central administration of arginine-vasopressin (AVP) in rodents has been associated with the modulation of a number of categories of behavior including social recognition and learning, aggression, grooming, and feeding. Concentrations of AVP in brain have also been functionally related to gonadal steroid hormone manipulations. In the current experiments we investigated the behavioral effects of centrally administered AVP on the behavior of pair-housed male squirrel monkeys during brief social separations. Prior to treatment, pairs of male squirrel monkeys established reliable and persistent dominance relationships measured as different patterns of social behavior and plasma levels of testosterone. Central administration of AVP increased scent-marking and grooming behaviors during the social separation test, however these effects were not influenced by the social status of the treated monkey. The effects of AVP on these measures were not mimicked by doses of oxytocin (OT). Both AVP and OT decreased the frequency of vigilance-checking and 'isolation-peep' calls. The data are consistent with a facilitatory role for AVP in the stress response and also suggest that these particular effects are not influenced by differences in testosterone associated with social dominance.

Analysis of Variance↗
PubMed1991

Comparative neuroanatomy of the sexually dimorphic hypothalamus in monogamous and polygamous voles.

In the present work we evaluated the degree of sexual dimorphism in two cell groups of the medial preoptic-anterior hypothalamus (MPOA-AH) in monogamous and polygamous voles. Quantitative determinations were made of volume, cell number, and cell density for the anteroventral-periventricular nucleus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN-POA). Polygamous montane voles (Microtus montanus) had a greater degree of sexual dimorphism in both cell groups than did monogamous prairie voles (M. ochrogaster). Most notable was the complete absence of the AVPV in male montane voles; male montane voles also had a significantly larger SDN-POA volume than did females. The only sexual dimorphism in prairie voles was a greater cell density in the female AVPV. In addition, prairie voles had larger relative brain size than did montane voles. Comparative behavioral studies have revealed a correlation between the degree of sexual dimorphism in external morphology and mating system, i.e., polygamous species display greater levels of dimorphism than do monogamous species. The present results indicate that the effects of sexual selection can also be seen in those brain regions, like the hypothalamus, that underlie social and reproductive behavior. Moreover, these results support the hypothesis that neuroanatomic dimorphisms in the MPOA-AH may be related to sex differences in behavior.

Animals↗
PubMed1991

Serotonergic modulation of the rat pup ultrasonic isolation call: studies with 5HT1 and 5HT2 subtype-selective agonists and antagonists.

A modulatory role for serotonin has been described for the development and expression of the ultrasonic 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗