title: Relationships among rat ultrasonic vocalizations, behavioral measures of striatal dopamine loss, and striatal tyrosine hydroxylase immunoreactivity at acute and chronic time points following unilateral 6-hydroxydopamine-induced dopamine depletion.
abstract: Voice deficits in Parkinson disease (PD) emerge early in the disease process, but do not improve with standard treatments targeting dopamine. Experimental work in the rat shows that severe and chronic unilateral nigrostriatal dopamine depletion with 6-OHDA results in decreased intensity, bandwidth, and complexity of ultrasonic vocalizations. However, it is unclear if mild/acute dopamine depletion, paralleling earlier stages of PD, results in vocalization deficits, or to what degree vocalization parameters are correlated with other dopamine-dependent indicators of lesion severity or percent of tyrosine hydroxylase (%TH) loss. Here, we assayed ultrasonic vocalizations, forelimb asymmetry, and apomorphine rotations in rats with a range of unilateral dopamine loss resulting from 6-OHDA or vehicle control infusions to the medial forebrain bundle at acute (72 h) and chronic (4 weeks) time points post-infusion. The %TH loss was evaluated at 4 weeks. At 72 h, forelimb asymmetry and %TH loss were significantly correlated, while at 4 weeks, all measures of lesion severity were significantly correlated with each other. Call complexity was significantly correlated with all measures of lesion severity at 72 h but only with %TH loss at 4 weeks. Bandwidth was correlated with forelimb asymmetry at both time points. Duration was significantly correlated with all dopamine depletion measures at 4 weeks. Notably, not all parameters were affected universally or equally across time. These results suggest that vocalization deficits may be a sensitive index of acute and mild catecholamine loss and further underscores the need to characterize the neural mechanisms underlying vocal deficits in PD.
authors.affiliation: Department of Surgery, Division of Otolaryngology, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Grant
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Barnett
authors.affiliation: Department of Surgery, Division of Otolaryngology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Emerald J
authors.initials: EJ
authors.lastname: Doll
authors.affiliation: Department of Surgery, Division of Otolaryngology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Glen
authors.initials: G
authors.lastname: Leverson
authors.affiliation: Department of Surgery, Division of Otolaryngology, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, WI 53706, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: Ciucci@surgery.wisc.edu.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ciucci
mesh_terms: D000208:Acute Disease; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002908:Chronic Disease; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000172:deficiency*; D018491:Dopamine Agonists / Q000494:pharmacology; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality; D008297:Male; D008474:Medial Forebrain Bundle; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation; D020318:Rats, Long-Evans; D012720:Severity of Illness Index; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000502:physiology*
chemical_list: D018491:Dopamine Agonists; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine
keywords: 6-OHDA; Dopamine; Parkinson disease; Rat; Striatum; Ultrasonic vocalization