Evidence for mediation of nociception by injection of the NK-3 receptor agonist, senktide, into the dorsal periaqueductal gray of rats

• Published in: Psychopharmacologia Vol. 204; no. 1; pp. 13 - 24
• Main Authors: Bassi, Gabriel S., Broiz, Ana C., Gomes, Margarete Z., Brandão, Marcus L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-05-2009; Springer; Springer Nature B.V
• Subjects: Animal behavior; Animals; Anxiety - physiopathology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain; Exploratory Behavior - drug effects; Fear - drug effects; Male; Maze Learning - drug effects; Medical sciences; Microinjections; Motor Activity - drug effects; Neurosciences; Neurotransmitters; Original Investigation; Pain Measurement; Peptide Fragments - pharmacology; Peptides; Periaqueductal Gray - metabolism; Pharmacology/Toxicology; Psychiatry; Psychopharmacology; Psychotropic drugs; Quinolines - pharmacology; Rats; Rats, Wistar; Receptors, Neurokinin-3 - agonists; Receptors, Neurokinin-3 - antagonists & inhibitors; Rodents; Substance P - analogs & derivatives; Substance P - pharmacology; Ultrasonics; Vocalization, Animal - drug effects; Ultrasonic vocalizations; Senktide; NK-3 receptors; Elevated plus maze; Dorsal periaqueductal gray; Nociception; Agonist; Rat; Sound production; Rodentia; Central nervous system; Encephalon; Vertebrata; Mammalia; Periaqueductal gray matter; Animal; NK3 Tachykinin receptor
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-008-1434-y

Rationale
Ultrasound vocalizations (USVs) at approximately 22 kHz are usual components of the defensive response of rats. However, depending on the neural substrate that is activated, such as the dorsal periaqueductal gray (dPAG), USV emissions may be reduced. Activation of neurokinin-1 (NK-1)-mediated mechanisms of the dPAG causes analgesia, reduced 22 kHz USVs, and anxiogenic-like effects in rats exposed to the elevated plus maze (EPM). Involvement of other types of neurokinin receptors in this activation has not yet been evaluated.
Objectives
The present study examined whether local injections of the selective NK-3 agonist senktide (1-100 pmol/0.2 μL) into the dPAG can (1) cause anxiogenic effects in the EPM, (2) influence novelty-induced 22 kHz USVs, or (3) change nociceptive reactivity in the tail-flick test.
Results
Senktide elicited a significant increase in exploratory behavior, an effect accompanied by hyperalgesia and an increase in the number of 22 kHz USVs. The nociceptive effects, increased locomotor activity, and USV emissions elicited by local injections of senktide (50 pmol/0.2 μL) were reduced by prior injections of the selective NK-3 receptor antagonist SB222200 (50 pmol/0.2 μL) into the dPAG.
Conclusions
These findings show that NK-3 receptors in the dPAG mediate nociceptive responses in this area, contrasting with the known fear-related processes mediated by NK-1 receptors in the dPAG. Both hyperalgesia and fear-related processes are accompanied by emissions of 22 kHz USVs.