Table 1.

Brief list of milestones of neuropharmacological studies of ultrasonic vocalizations in the rat signalling emotional states

Pharmacological and Related Findings	Agents Used	References
22 kHz ultrasonic vocalizations are induced from the rat hypothalamic-preoptic area by cholinergic stimulation.	carbachol, atropine	[23, 59, 136]
The magnitude of the 22 kHz ultrasonic response is dose-dependent and antagonized by muscarinic antagonist.	carbachol, atropine	[23, 136]
22 kHz vocalizations, induced by carbachol from septum and antagonised by antimuscarinic agent, are initiated by direct cholinergic input from the laterodorsal tegmental nucleus.	carbachol, atropine, scopolamine, glutamate	[24, 147]
22 kHz vocalization responses are mapped in the rat brain and form the medial cholinoceptive (responding to acetylcholine) vocalization strip along the neuraxis.	carbachol, atropine	[24, 93, 136]
22 kHz vocalizations induced from the laterodorsal tegmental nucleus by glutamate are antagonized by scopolamine injected into hypothalamic-preoptic area (part of the strip).	glutamate, atropine, scopolamine	[24, 137]
The ascending mesolimbic cholinergic system originating from the laterodorsal tegmental nucleus is postulated.	carbachol, scopolamine, glutamate	[146, 147]
Cholinergic neurons of the laterodorsal tegmental nucleus are active during emission of 22 kHz vocalizations.	carbachol	[149]
The mesolimbic cholinergic system that originates from tegmentum, induces negative emotional state. 22 kHz vocalizations signal negative emotional state.		[9, 24, 29, 79, 80, 89, 93, 144, 147
50 kHz vocalizations are induced by glutamate, but not carbachol, from the rat brain.	glutamate, carbachol	[148]
50 kHz ultrasonic vocalizations induced by intracerebral glutamate are antagonized by systemic haloperidol.	glutamate, haloperidol	[113]
50 kHz vocalizations are induced by amphetamine and the responses are mapped in the nucleus accumbens.	amphetamine	[20, 22, 45, 112]
Amphetamine-induced 50 kHz vocalizations are dose dependent and antagonized by dopamine antagonists.	amphetamine, raclopride, SKF-83566	[20, 45, 112]
50 kHz vocalizations are induced by other dopaminergic agents (given systemically or intracerebrally).	cocaine, methylphenidate, apomorphine, quinpirole	[21, 22, 110, 134]
50 kHz vocalizations are induced by release of dopamine in the nucleus accumbens from the mesolimbic dopamine system originating from the ventral tegmental area.		[9, 39, 42, 43]
Emission of the 50 kHz vocalization signals positive emotional state.		[9, 29, 32, 39, 40, 89, 125, 142, 143]
50 kHz vocalizations are divided into subtypes: flat calls, and frequency-modulated calls with steps and/or trills. The subtypes are postulated to have behavioral significance.		[28, 32, 104, 110, 124, 126]
Replay of 50 kHz vocalizations is self-administered by rats.		[32]
The system for negative emotional state signaled by 22 kHz calls and the system for positive emotional state signaled by 50 kHz calls are functionally antagonistic to each other.	carbachol, amphetamine	[9, 24, 143]
Positive or negative emotional arousal is initiated by two ascending reticular activating subsystems: mesolimbic dopaminergic subsystem or mesolimbic cholinergic subsystem, respectively.		[144]

The table summarizes main neuropharmacological and related studies of ultrasonic vocalizations in the rat that are associated with signalling negative and positive emotional states. Studies on other species are not included. The milestones of the studies are not necessarily organized in chronological order but reflect the progression of findings and ideas over the last 25 years. Main references indicate selected papers cited in this review only, and are neither organized in chronological order nor form a complete list. Many details of the studies were omitted, for example studies of receptor subtypes or many studies of acoustic details of the calls.