Jeffrey Burgdorf
Northwestern University
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Featured researches published by Jeffrey Burgdorf.
Behavioural Brain Research | 2007
Jeffrey Burgdorf; Paul L. Wood; Roger A. Kroes; Joseph R. Moskal; Jaak Panksepp
Fifty-kHz ultrasonic vocalizations have been proposed to reflect a positive appetitive affective state in rats, being consistently linked to the positive appetitive behavior. In the first study, we examined the brain substrates of 50-kHz ultrasonic vocalizations (USVs) by using localized electrical stimulation of the brain (ESB) at various sites that are known to mediate reward. We found that the brain areas that produced ESB-induced 50-kHz calls are the areas that have previously been shown to support the most vigorous self-stimulation behavior (prefrontal cortex, nucleus accumbens, ventral pallidum, lateral preoptic area, lateral hypothalamus, ventral tegmental area, and raphe). Importantly, all animals that showed repeatable ESB-induced 50-kHz USVs demonstrated self-stimulation behavior. In the second study, conditioned place preference was assessed following microinjection of the mu-opiate agonist Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAMGO) directly into the ventral tegmental area (VTA) at a dose previously found to be rewarding. Animals that showed more 50-kHz USVs in response to drug injections compared to vehicle injections showed significant place preferences, whereas animals that did not show elevated vocalization to DAMGO did not show place preference. In experiment 3, we examined the effect of VTA electrolytic lesions, 6-OHDA lesions, and the effect of the D1/D2 dopamine antagonist flupenthixol (0 and 0.8 mg/kg, i.p.) on 50-kHz ultrasonic vocalizations. We found that these manipulations all selectively reduced 50-kHz ultrasonic vocalizations, and that these effects could be disassociated from any side effects. These data are consistent with the proposition that 50-kHz calls are tightly linked to reward in rats and that the neural circuit of 50-kHz calls closely overlaps that of ESB self-stimulation reward, drug reward, and the mesolimbic dopamine system.
Neuroscience & Biobehavioral Reviews | 2006
Jeffrey Burgdorf; Jaak Panksepp
Compared to the study of negative emotions such as fear, the neurobiology of positive emotional processes and the associated positive affect (PA) states has only recently received scientific attention. Biological theories conceptualize PA as being related to (i) signals indicating that bodies are returning to equilibrium among those studying homeostasis, (ii) utility estimation among those favoring neuroeconomic views, and (iii) approach and other instinctual behaviors among those cultivating neuroethological perspectives. Indeed, there are probably several distinct forms of positive affect, but all are closely related to ancient sub-neocortical limbic brain regions we share with other mammals. There is now a convergence of evidence to suggest that various regions of the limbic system, including especially ventral striatal dopamine systems are implemented in an anticipatory (appetitive) positive affective state. Dopamine independent mechanisms utilizing opiate and GABA receptors in the ventral striatum, amygdala and orbital frontal cortex are important in elaborating consummatory PA (i.e. sensory pleasure) states, and various neuropeptides mediate homeostatic satisfactions.
Journal of Comparative Psychology | 1998
Brian Knutson; Jeffrey Burgdorf; Jaak Panksepp
The authors provide initial documentation that juvenile rats emit short, high-frequency ultrasonic vocalizations (high USVs, approximately 55 kHz) during rough-and-tumble play. In an observational study, they further observe that these vocalizations both correlate with and predict appetitive components of the play behavioral repertoire. Additional experiments characterized eliciting conditions for high USVs. Without prior play exposure, rats separated by a screen vocalized less than playing rats, but after only 1 play session, separated rats vocalized more than playing rats. This findings suggested that high USVs were linked to a motivational state rather than specific play behaviors or general activity. Furthermore, individual rats vocalized more in a chamber associated with play than in a habituated control chamber. Finally, congruent and incongruent motivational manipulations modulated vocalization expression. Although play deprivation enhanced high USVs, an arousing but aversive stimulus (bright light) reduced them. Taken together, these findings suggest that high USVs may index an appetitive motivation to play in juvenile rats.
Physiology & Behavior | 2003
Jaak Panksepp; Jeffrey Burgdorf
Paul MacLeans concept of epistemics-the neuroscientific study of subjective experience-requires animal brain research that can be related to predictions concerning the internal experiences of humans. Especially robust relationships come from studies of the emotional/affective processes that arise from subcortical brain systems shared by all mammals. Recent affective neuroscience research has yielded the discovery of play- and tickle-induced ultrasonic vocalization patterns ( approximately 50-kHz chirps) in rats may have more than a passing resemblance to primitive human laughter. In this paper, we summarize a dozen reasons for the working hypothesis that such rat vocalizations reflect a type of positive affect that may have evolutionary relations to the joyfulness of human childhood laughter commonly accompanying social play. The neurobiological nature of human laughter is discussed, and the relevance of such ludic processes for understanding clinical disorders such as attention deficit hyperactivity disorders (ADHD), addictive urges and mood imbalances are discussed.
Behavioural Brain Research | 2000
Jaak Panksepp; Jeffrey Burgdorf
In these studies the incidence of conditioned and unconditioned 50-kHz ultrasonic vocalizations (USVs) in young rats was measured in response to rewarding manual tickling by an experimenter. We found that isolate-housed animals vocalize much more then socially housed ones, and when their housing conditions are reversed, they gradually shift their vocalization tendencies. Isolate-housed animals also show quicker acquisition of instrumental tasks for tickling, and exhibit less avoidance of tickling as compared to socially housed Ss. Isolate-housed animals also show rapid acquisition of 50-kHz USVs to a conditioned stimulus that predicts tickle reward, while socially housed animals do not. We successfully bred for high and low vocalization rates in response to tickling within four generations. The high tickle line showed quicker acquisition of an instrumental task for, as well as less avoidance of, tickling as compared to the random and low tickle lines. They also played more. Lastly, we found that the glutamate antagonist MK-801 can reduce tickle-induced 50-kHz USVs, but is resistant to opioid, dopamine and cholinergic stimulant and blocking agents. Overall, these results suggest that tickle evoked 50-kHz USVs may be a useful behavioral marker of positive social affect in rats. Difficulties with such concepts are also discussed.
Behavioral Neuroscience | 2000
Jeffrey Burgdorf; Brian Knutson; Jaak Panksepp
Adult rats emit increased rates of 50-kHz ultrasonic vocalizations (USVs) before receiving social and pharmacological rewards. This study sought to determine whether anticipation of rewarding electrical stimulation of the brain (ESB) would also elicit these vocalizations. In Experiments 1 and 2, rats showed increased 50-kHz USVs before receiving experimenter-delivered ventral tegmental area (VTA) and lateral hypothalamic (LH) ESB on a fixed time 20-s schedule. In Experiments 3 and 4, rats increased their rate of 50-kHz USVs in response to cues that predicted the opportunity to self-stimulate the VTA or LH. Interestingly, unexpected termination of either type of ESB evoked 20-kHz, rather than 50-kHz, USVs. In Experiment 5, a cue that predicted daily 1-hr feeding sessions increased 50-kHz USVs, whereas a cue that predicted footshock decreased 50-kHz USVs. These effects could not be explained simply by changes in locomotor activity or general arousal. Together, these findings support the hypothesis that short 50-kHz USVs may selectively index a state of reward anticipation in rats.
Physiology & Behavior | 2001
Jeffrey Burgdorf; Jaak Panksepp
In adolescent rats, 50-kHz vocalizations are most evident during tickling and rough-and-tumble play. The following experiments evaluated whether 50-kHz vocalizations reflect positive social affect by determining (1) if tickling is a rewarding event, (2) if social or isolate housing conditions differentially influence the response (since housing condition has been found to effect the reward magnitude of social encounters), and (3) if drugs that work on mu-opiate receptors, which has been hypothesized to control positive social affect, modulate tickling. Tickling was positively reinforcing as demonstrated by elevated operant behavior, conditioned place preference, and approach measures. A significant negative correlation between vocalization rate and approach latency measures was found. Social housing reduced tickle-induced vocalizations and approach speeds compared to isolate housing. Naloxone (1 mg/kg) increased vocalization in the socially housed rats and decreased it in isolated Subjects (Ss). These findings suggest that tickling can be used to induce positive social affect in rodents, and that it is modulated by endogenous opioids.
Neuropsychopharmacology | 2013
Jeffrey Burgdorf; Xiao-lei Zhang; Katherine L. Nicholson; Robert L. Balster; J. David Leander; Patric K. Stanton; Amanda L. Gross; Roger A. Kroes; Joseph R. Moskal
Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity’ by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression.
Neuroscience & Biobehavioral Reviews | 2011
Jeffrey Burgdorf; Jaak Panksepp; Joseph R. Moskal
The evidence that frequency modulated (FM) 50 kHz ultrasonic vocalizations (USVs) reflect a positive emotional state in rats is reviewed. Positive emotional states in humans are measured by facial-vocal displays (e.g., Duchenne smiling and laughter), approach behavior, and subjective self-report of feeling states. In laboratory animals, only facial-vocal displays, along with approach behavior can be measured. FM 50 kHz USVs are uniquely elevated by hedonic stimuli and suppressed by aversive stimuli. Rates of FM 50 kHz USVs are positively correlated to the rewarding value of the eliciting stimulus. Additionally, playbacks of these vocalizations are rewarding. The neural and pharmacological substrates of 50 kHz USVs are consistent with those of human positive affective states. By experimentally eliciting FM 50 kHz USVs, the novel molecular underpinning of positive affect can be elucidated and may be similar to those in humans. In humans, positive emotional states confer resilience to depression and anxiety, as well as promote overall health. Using rough-and-tumble play induced hedonic USVs, we have identified insulin like growth factor I and the NR2B subunit of the NMDA receptor as playing a functional role in positive affective states. From this research, we have developed a promising new class of antidepressants that is entering phase II clinical trials for the treatment of depression.
PLOS ONE | 2008
Haoran Wang; Shuyin Liang; Jeffrey Burgdorf; Jürgen Wess; John S. Yeomans
Adult mice communicate by emitting ultrasonic vocalizations (USVs) during the appetitive phases of sexual behavior. However, little is known about the genes important in controlling call production. Here, we study the induction and regulation of USVs in muscarinic and dopaminergic receptor knockout (KO) mice as well as wild-type controls during sexual behavior. Female mouse urine, but not female rat or human urine, induced USVs in male mice, whereas male urine did not induce USVs in females. Direct contact of males with females is required for eliciting high level of USVs in males. USVs (25 to120 kHz) were emitted only by males, suggesting positive state; however human-audible squeaks were produced only by females, implying negative state during male-female pairing. USVs were divided into flat and frequency-modulated calls. Male USVs often changed from continuous to broken frequency-modulated calls after initiation of mounting. In M2 KO mice, USVs were lost in about 70–80% of the mice, correlating with a loss of sexual interaction. In M5 KO mice, mean USVs were reduced by almost 80% even though sexual interaction was vigorous. In D2 KOs, the duration of USVs was extended by 20%. In M4 KOs, no significant differences were observed. Amphetamine dose-dependently induced USVs in wild-type males (most at 0.5 mg/kg i.p.), but did not elicit USVs in M5 KO or female mice. These studies suggest that M2 and M5 muscarinic receptors are needed for male USV production during male-female interactions, likely via their roles in dopamine activation. These findings are important for the understanding of the neural substrates for positive affect.