Adult rat ultrasonic vocalizations and reward: Effects of propranolol and repeated cocaine administration.

BACKGROUND: Mechanisms underlying psychostimulant euphoria remain poorly understood. In adult rats, positive emotional states are associated with alterations in 50-kHz ultrasonic vocalizations (USVs): specifically, "trill" calls are promoted over "flat" calls. Here, we investigated the effects of acute and repeated cocaine administration, and-based on previous findings with amphetamine-their possible dependence on beta-adrenergic receptors. METHODS: Adult male Long-Evans rats received intraperitoneal drug or saline injections before daily USV recording. Fourteen 50-kHz call subtypes were analyzed. In Experiments 1 and 2, cocaine (1-10 mg/kg) and propranolol (10 mg/kg) were tested alone. In Experiment 3, propranolol/cocaine interactions were sought within a conditioned place preference (CPP) procedure. Experiment 4 investigated acute and chronic cocaine effects (Phase 1), and propranolol/cocaine interactions either in an open field (Phase 2) or within a CPP procedure (Phase 3). RESULTS: In drug-naïve animals, cocaine increased the 50-kHz call rate, with sensitization developing rapidly. After more extended exposure, cocaine now also increased the relative prevalence of trill versus flat calls; effects on other subtypes were also revealed. The beta-blocker propranolol prevented neither cocaine CPP nor cocaine effects on USV emission or locomotion but exerted significant USV-related effects when given alone. CPP magnitude and USV-related measures were uncorrelated. CONCLUSIONS: With long-term intraperitoneal administration, cocaine can alter the relative prevalence of several 50-kHz call subtypes; its ability to promote trill versus flat calls, in particular, is consistent with a positive affect interpretation. Cocaine's behavioral effects (i.e., USV-related, locomotor, CPP) appear independent of beta-adrenergic receptor activity.

Stable long-term individual differences in 50-kHz vocalization rate and call subtype prevalence in adult male rats: Comparisons with sucrose preference.

Sucrose preference (SP) is a widely used measure of anhedonia in rat models of depression, yet depressed patients do not reliably show an analogous deficit. As an alternative affect-related measure, adult rat ultrasonic vocalizations (USVs) are attracting interest, but it is unclear whether SP and USVs provide independent measures. Here, we have assessed whether SP and USV emission are correlated in the absence of a depressogenic procedure. To this end, 24 male Long-Evans rats were tested daily for 24 days, with alternating SP tests and USV recordings; after a 3-month hiatus, USV emission was re-evaluated for 6 more days. SP was measured in simultaneous two-bottle choice tests, and USVs were recorded in an open field. The main measures were: SP, 50-kHz call rate, and relative prevalence of trill and flat call subtypes. These measures showed temporally-stable individual differences across the initial 24-day testing period, and at the 3-month USV follow-up tests. Correlational analysis revealed no significant relationships between SP and the three main USV measures. Rats differed consistently, not only in their 50-kHz call rates but also in their 50-kHz call profiles (i.e., the relative prevalence of 14 call subtypes); most rats preferentially emitted either trill or flat calls. Several inter-call subtype associations were detected, including a strong negative relationship between the relative prevalence of flat and trill calls. The 50-kHz call rate was correlated with the relative prevalence of only one call subtype (short calls, negative correlation), but was positively correlated with absolute emission rates for almost all subtypes. In conclusion, adult rats exhibited temporally-stable individual differences over weeks (SP) or months (USVs) of testing. This trait-like stability helped to reveal a lack of relationship between SP and the USV-related variables under study, suggesting that these measures may capture different constructs of possible relevance to animal models of depression.

G protein-coupled estrogen receptor-1 enhances excitatory synaptic responses in the entorhinal cortex.

Activation of estrogen receptors is thought to modulate cognitive function in the hippocampus, prefrontal cortex, and striatum by affecting both excitatory and inhibitory synaptic transmission. The entorhinal cortex is a major source of cortical sensory and associational input to the hippocampus, but it is unclear whether either estrogens or progestogens may modulate cognitive function through effects on synaptic transmission in the entorhinal cortex. This study assessed the effects of the brief application of either 17-ß estradiol (E2) or progesterone on excitatory glutamatergic synaptic transmission in the female rat entorhinal cortex in vitro. Rats were ovariectomized on postnatal day (PD) 63 and also received subdermal E2 implants to maintain constant low levels of circulating E2 on par with estrus. Electrophysiological recordings from brain slices were obtained between PD70 and PD86, and field excitatory postsynaptic potentials (fEPSPs) reflecting the activation of the superficial layers of the entorhinal cortex were evoked by the stimulation of layer I afferents. The application of E2 (10 nM) for 20 min resulted in a small increase in the amplitude of fEPSPs that reversed during the 30-min washout period. The application of the ERα agonist propylpyrazoletriol (PPT) (100 nM) or the ß agonist DPN (1 µM) did not significantly affect synaptic responses. However, the application of the G protein-coupled estrogen receptor-1 (GPER1) agonist G1 (100 nM) induced a reversible increase in fEPSP amplitude similar to that induced by E2. Furthermore, the potentiation of responses induced by G1 was blocked by the GPER1 antagonist G15 (1 µM). Application of progesterone (100 nM) or its metabolite allopregnanolone (1 µM) did not significantly affect synaptic responses. The potentiation of synaptic transmission in the entorhinal cortex induced by the activation of GPER1 receptors may contribute to the modulation of cognitive function in female rats.