Individual differences in frequency modulated 50-kHz ultrasonic vocalizations reflect but do not predict cocaine self-administration in rats.

The antagonistic relationship between aversive and appetitive emotional states in rats as studied by pharmacologically-induced ultrasonic vocalization from the nucleus accumbens and lateral septum

Playback of 22-kHz and 50-kHz ultrasonic vocalizations induces differential c-fos expression in rat brain

Frequency-modulated 50-kHz ultrasonic vocalizations (USVs) are emitted by adult rats in response to psychostimulants and non-pharmacological appetitive stimuli and thus have been proposed to model positive affect. The main aim was to determine whether rewarding doses of morphine increase 50-kHz call rate or alter the relative prevalence of the trill call subtype. In experiment 1, USVs were recorded from adult male Long-Evans rats after subchronic morphine (1mg/kg subcutaneous (SC)) administration, acute challenge with morphine (1 and 3mg/kg SC) or amphetamine (1mg/kg IP, positive control), and in conjunction with locomotor activity tests with morphine (1 and 3mg/kg SC). In experiments 2 and 3, the USV altering, rewarding, and locomotor effects of morphine were examined using a conditioned place preference (CPP) procedure. In experiment 1, morphine (1mg/kg) initially suppressed calling; rats became tolerant to this effect with repeated exposure. Tested subsequently in singly- and pair-tested rats, morphine markedly decreased USVs but significantly increased locomotor activity. In experiments 2 and 3, morphine produced a significant CPP without increasing either unconditioned or conditioned USV emission. Morphine did not detectably alter the relative prevalence of 50-kHz call subtypes. Although 50-kHz calls, and the trill call subtype in particular, have been proposed as an animal model of positive mood, not all euphoriant drugs acutely increase the rate of 50-kHz calling or consistently promote trill calls.

Chapter 39 - Ultrasonic Vocalizations in Rats as a Measure of Emotional Responses to Stress: Models of Anxiety and Depression

Sex Differences and Hormonal Influences on Acquisition of Cocaine Self-Administration in Rats

Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats.

Suppression of morphine and cocaine self-administration in rats by a mixed mu antagonist-kappa agonist (N-CBM-TAMO) and a long-acting selective D 1 antagonist (AS-300)

The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats

Wheel-running attenuates intravenous cocaine self-administration in rats: Sex differences

Contrasting the reinforcing effects of the novel dopamine transport inhibitors JJC8-088 and JJC8-091 in monkeys: Potential translation to medication assisted treatment

Effects of neonatal dopaminergic lesion on oral cocaine self-administration in rats: Higher female vulnerability to cocaine consumption

Progesterone decreases cocaine self-administration in women and in female rats. In a previous study using rats selectively bred for high (HiS) or low (LoS) saccharin intake, HiS rats escalated their cocaine intake compared with LoS rats. Our goal was to examine the effects of progesterone on the escalation of cocaine self-administration in HiS and LoS rats. Four groups of female rats were compared: HiS P (progesterone treated), LoS P, HiS VEH (vehicle treated), and LoS VEH. Rats were trained to self-administer 0.8 mg/kg cocaine intravenously under a fixed-ratio 1 schedule during daily short-access (ShA) 2-h sessions. Rats then self-administered three randomly-presented doses of cocaine (0.2, 0.4, and 1.6 mg/kg), and then had daily 6-h long-access (LgA) sessions with 0.4 mg/kg of cocaine for 21 days. Cocaine intake was then reassessed with the four doses under the ShA condition. Throughout the experiment, rats were treated with daily subcutaneous injections of progesterone (0.5 mg/kg) or an equal volume of vehicle 30 min before each session. During the initial ShA condition, HiS rats earned more cocaine infusions than LoS rats at all doses, and during the subsequent LgA condition, HiS rats escalated cocaine intake, whereas the LoS rats maintained a steady rate. Progesterone treatment potentiated escalation of cocaine intake in the HiS rats but had an opposite effect on LoS rats, attenuating their cocaine self-administration. Results from the post-LgA dose-response ShA condition indicated that both LoS and HiS vehicle-treated and progesterone-treated rats earned more infusions than pre-LgA, but mainly at low doses. These results suggest that genetic differences in drug abuse vulnerability contribute differentially to treatment outcomes during escalation, a critical phase of the drug abuse process.

Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models. Fifty kilohertz ultrasonic vocalizations (USVs) were recorded as an index of positive affect throughout experiments. In Experiment 1, MDPV and cocaine dose-dependently elicited 50-kHz USVs upon systemic injection, but MDPV increased USVs at greater rates and with greater persistence relative to cocaine. In Experiment 2, latency to begin MDPV self-administration was shorter than latency to begin cocaine self-administration, and self-administered MDPV elicited greater and more persistent rates of 50-kHz USVs versus cocaine. MDPV-elicited 50-kHz USVs were sustained over the course of drug load-up whereas cocaine-elicited USVs waned following initial infusions. Notably, we observed a robust presence of context-elicited 50-kHz USVs from both MDPV and cocaine self-administering rats. Collectively, these data suggest that MDPV has powerfully rewarding and reinforcing effects relative to cocaine at one-tenth doses. Consistent with prior work, we additionally interpret these data in supporting that MDPV has significant abuse risk based on its potency and subjectively positive effects. Future studies will be needed to better refine therapeutic strategies targeted at reducing the rewarding effects of cathinone analogs in efforts to ultimately reduce abuse liability.

Xanomeline treatment attenuates cocaine self-administration in rats and nonhuman primates.

Antagonistic allosteric A2AR-D2R receptor-receptor interactions in heteroreceptor complexes counteract cocaine self-administration and cocaine seeking in rats as seen in biochemical and behavioral experiments. It was shown that the human A2AR transmembrane five (TM5) was part of the interface of the human A2AR-D2R receptor heteromer. In the current paper, the rat A2AR synthetic TM5 (synthTM5) peptide disrupts the A2AR-D2R heteroreceptor complex in HEK293 cells as shown by the bioluminescence resonance energy transfer method. Rat A2AR synthTM5 peptide, microinjected into the nucleus accumbens, produced a complete counteraction of the inhibitory effects of the A2AR agonist CGS21680 on cocaine self-administration. It was linked to a disappearance of the accumbal A2AR-D2R heteroreceptor complexes and the A2AR agonist induced inhibition of D2R recognition using proximity ligation assay and biochemical binding techniques. However, possible effects of the A2AR synthTM5 peptide on accumbal A2AR-D3R and A2AR-D4R heteroreceptor complexes remain to be excluded. Evidence is provided that accumbal A2AR-D2R-like heteroreceptor complexes with their antagonistic receptor-receptor interactions can be major targets for treatment of cocaine use disorder.