α- and β-Adrenergic Receptors Differentially Modulate the Emission of Spontaneous and Amphetamine-Induced 50-kHz Ultrasonic Vocalizations in Adult Rats

Amphetamine (AMPH) increases adult rat 50-kHz ultrasonic vocalizations, preferentially promoting frequency-modulated (FM) calls that have been proposed to reflect positive affect. The main objective of this study was to investigate a possible noradrenergic contribution to AMPH-induced calling. Adult male Long-Evans rats were tested with AMPH (1 mg/kg intraperitoneal) or saline combined with various systemic pretreatments: clonidine (alpha 2 adrenergic agonist), prazosin (alpha 1 antagonist), atipamezole (alpha 2 antagonist), propranolol, betaxolol, and/or ICI 118,551 (beta 1/beta 2, beta 1, and beta 2 antagonists, respectively), nadolol (beta 1/beta 2 antagonist, peripheral only), or NAD-299 (5HT(1A) antagonist). In addition, effects of cirazoline (alpha 1 adrenergic agonist) and cocaine (0.25-1.5 mg/kg intravenous) were studied alone. AMPH-induced calling was suppressed by low-dose clonidine and prazosin. Cirazoline and atipamezole did not significantly affect calling rate. Propranolol, without affecting the call rate, dose dependently promoted 'flat' calls under AMPH while suppressing 'trills,' thus reversing the effects of AMPH on the 'call subtype profile.' This effect of propranolol seemed to be mediated by simultaneous inhibition of CNS beta 1 and beta 2 rather than by 5HT(1A) receptors. Finally, cocaine elicited fewer calls than did AMPH, but produced the same shift in the call subtype profile. Taken together, these results reveal differential drug effects on flat vs trill vs other FM 50-kHz calls. These findings highlight the value of detailed call subtype analyses, and show that 50-kHz calls are associated with adrenergic alpha 1- and beta-receptor mechanisms. These preclinical findings suggest that noradrenergic contributions to psychostimulant subjective effects may warrant further investigation. Neuropsychopharmacology (2012) 37, 808-821; doi: 10.1038/npp.2011.258; published online 26 October 2011