The Role of Dopaminergic Transmission Through D1-like and D2-like Receptors in Amphetamine-induced Rat Ultrasonic Vocalizations

Rationale: Systemic amphetamine (AMPH) administration increases the rate of 50-kHz ultrasonic vocalizations (USVs) in adult rats and preferentially enhances the 'trill' subtype; these effects of AMPH critically depend on noradrenergic transmission, but the possible contributions of dopamine are unclear.

Objective: To assess the role of dopamine in 50-kHz USVs emitted drug-free and following systemic AMPH administration.

Methods: Adult male Long-Evans rats pre-selected for high AMPH-induced calling rates were tested with AMPH (1 mg/kg, intraperitoneal (IP)) and saline following pretreatment with the following dopamine receptor antagonists: SCH 23390 (0.005-0.02 mg/kg, subcutaneous (SC)), SCH 39166 (0.03-0.3 mg/kg, SC), haloperidol (0.1, 0.2 mg/kg, IP), sulpiride (20-80 mg/kg, SC), raclopride (0.1-0.5 mg/kg, SC), clozapine (4 mg/kg, SC), risperidone (0.5 mg/kg, SC), and pimozide (1 mg/kg, IP). The dopamine and noradrenaline reuptake inhibitors (GBR 12909 and nisoxetine, respectively) were also tested, alone and in combination.

Results: SCH 23390, SCH 39166, haloperidol, and raclopride dose-dependently inhibited vocalizations under AMPH and suppressed the proportion of trill calls. Sulpiride, however, had no discernable effect on call rate or profile, even at a high dose that reduced locomotor activity. Single doses of clozapine, risperidone, and pimozide all markedly decreased calling under saline and AMPH. Finally, GBR 12909 and nisoxetine failed to promote 50-kHz USVs detectably or alter the subtype profile, when tested alone or in combination.

Conclusions: The rate of 50-kHz USVs and the call subtype profile following systemic AMPH administration depends on dopaminergic neurotransmission through D1-like and D2-like receptors. However, inhibiting dopamine and/or noradrenaline reuptake appears insufficient to induce calling.