Showing papers by "Brian Knutson published in 1997"

Effects of Serotonin Depletion on the Play of Juvenile Rats

Abstract: Rough-and-tumble play presents opportunities for young mammals to test social skills in an affiliative context. Because serotonin (5HT) depletion can induce nonaffiliative or openly hostile behavior in adult rats’ and primates,’ we conducted an experiment to examine if serotonin depletion would also increase the agonistic nature of play behavior in juvenile rats. At both 16 and 23 days of age, 26 rats received serotonin lesions via central (third ventricle) injections of 7.5 p,l of 75 p,g of 5,7 dihydroxytryptamine (a serotonin neurotoxin) mixed in 0.9% saline solution with 0.1% ascorbic acid. A control group of 26 rats received sham lesions and injections of vehicle. All rats received desiprimine (25 mgkg i.p.) 30 minutes before surgery and nomifensine (25 mgkg i.p.) 20 minutes before surgery to spare noradrenergic and dopaminergic neurons from damage. Ten days after the second lesion treatment, rats were matched into one of three types of play pairs: (1) sham + sham (Sham), (2) sham + 5HT lesioned (Mixed), or (3) 5HT lesioned + 5HT lesioned (5HT-lesioned). Play behaviors for each partner were recorded during daily 5-minute play sessions (pins and dorsal contacts), which spanned 8 days. The partner who pinned most during the first three play sessions was deemed the “dominant” partner for that pair. Analyses of individual data revealed that dominant 5HT-lesioned rats made more dorsal contacts, whereas nondominant 5HT-lesioned rats made fewer dorsal contacts than did sham-lesioned controls (F (7,336) = 3.09, p < 0.005; FIG. 1). Furthermore, dominant rats continued to pin more than did nondominant rats following the first 3 days of play (F (1,48) = 10.87, p < 0.005); however, this effect diminished over time (F (7,336) = 6.42, p c 0.001) and interacted with the 5HT lesion, such that 5HT-lesioned dominant rats pinned more during the last 3 days of play, whereas 5HT-lesioned nondominant rats consistently pinned less than did the Sham-lesioned controls (F (4,192) = 2.59, p < 0.05; FIG. 2). These patterns of results were further supported by pairwise analyses, which examined behavioral asymmetries within each play pair. Specifically, 5HT-lesioned pairs showed the most dorsal contact asymmetry (mean 2 SEM = 0.27 2 0.05), whereas Mixed pairs showed less (0.18 +0.04) and Sham pairs showed the least (-0.03 2 0.02; F (2,23) = 4.61, p < 0.025). Furthermore, 5HT-lesioned and Mixed

Serotonergic Intervention Increases Affiliative Behavior in Humans

Abstract: Increased serotonergic activity has been linked to affiliative behavior in groupliving primates. For example, cerebrospinal 5-hydroxyindoleacetic acid (a serotonin metabolite) is correlated with time spent grooming others, time spent in close proximity to others, and mean number of neighbors within a 5-mile radius in free-ranging macaques.' Furthermore, serotonergic augmentation increases the approach, grooming, and proximity of captive vervets.* Despite these suggestive findings, there are no data to indicate whether serotonin augmentation increases affiliative behavior in normal humans. To address this question, a serotonin-selective reuptake inhibitor (paroxetine, SmithKline Beecham; 20 mg/day PO; IZ = 28) or placebo (n = 25) was given to 47 young adults in a fully randomized double-blind experiment. Changes in affiliative behavior were assessed in the context of a collaborative puzzle-solving task. All participants were screened to exclude concurrent medications, preexisting personal or familial psychopathology, and prior substance abuse (SCID-NP). Compliance and circulating blood levels of the medication were checked by paroxetine assay of blood samples collected at the study's conclusion. Interactive behavior during a puzzle task was videotaped at baseline, at 1 week of treatment, and at 4 weeks of treatment. Seated subject pairs completed a 10-minute task requiring the arrangement of tangram pieces to match a target figure. Rules stated that only one member of the pair could touch the pieces at a time. Each subject pair included one partner in the paroxetine condition and one in the placebo condition, with different pairings of partners each week. Videotaped behaviors (grasping puzzle pieces, giving verbal commands, and making verbal suggestions) were coded by blind raters, who demonstrated satisfactory interrater agreement (mean interrater r = 0.72, p < 0.001). Relative to placebo controls, paroxetine-treated individuals showed increasing affiliative behavior (aggregate measure: suggestions-commands-grasps) from baseline to the treatment period (+ 0.27 SD paroxetine vs -0.46 SD placebo, p c 0.05).