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Cocaine Dose (cocaine + dose)
Selected AbstractsAlcohol, Cocaine, and Brain Stimulation-Reward in C57Bl6/J and DBA2/J MiceALCOHOLISM, Issue 1 2010Eric W. Fish Background:, Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine. Methods:, Male C57 and DBA mice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift method, the BSR threshold (,0) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally. Results:, In C57 mice, the 0.6 g/kg dose of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBA mice, alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBA mice than in C57 mice as revealed by a leftward shift in the cocaine dose,response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates. Conclusions:, In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBA mice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique. [source] SAFETY OF DEXTROAMPHETAMINE AND COCAINE COMBINATIONS IN COCAINE USERSALCOHOLISM, Issue 2008William Murff Two studies evaluated the safety and abuse liability of d-amphetamine in combination with cocaine in twenty cocaine-using research volunteers maintained in a controlled research laboratory. The first study tested low doses of d-amphetamine (15 mg) administered orally as a 1.5-hr pretreatment before low intranasal doses (48 mg) of cocaine. The study was double-blind, double-dummy, and placebo-controlled. A dose run-up procedure was employed to maximize safety. All drug effects were modest and the main finding of the study was diminished subjective effects of cocaine on a replicate determination of the original cocaine dose. The second study examined higher doses of d-amphetamine (30 mg, p.o.) and cocaine (96 mg, i.n.), alone and in combination, without a gradual dose run-up. Cocaine alone increased subjective mood, cocaine craving, and ratings indicating cocaine abuse potential. Again, replicate administration of cocaine produced lesser subjective effects than the first dose. D-amphetamine alone increased systolic and mean arterial pressures, but produced minimal effects on subjective mood. The combination of d-amphetamine and cocaine never produced effects greater than cocaine alone except for one subject who had an asymptomatic hypertensive episode. The data are interpreted in light of the possible use of stimulants for the treatment of cocaine dependence. [source] Extremely low frequency magnetic field effects on premorbid behaviors produced by cocaine in the mouseBIOELECTROMAGNETICS, Issue 4 2004Jungdae Kim Abstract We investigated the premorbid behavioral changes produced by the administration of cocaine and acute exposure to extremely low frequency (ELF) magnetic field (MF) in the mouse. ICR mice received intraperitoneal injections of cocaine at two doses (65 and 70 mg/kg) and were subsequently exposed to one of eight ELF-MF fields (2, 3, 4, 8, 10, 15, 25, or 60 Hz) of about 20 G (2 mT) intensity immediately after injection. Twelve mice were used for each of applied cocaine dose and ELF-MF level. For a given dose of cocaine, the applied MF frequencies were randomly ordered, and blind tests were carried out in which the behavior observer did not know the frequencies of MF. The premorbid behaviors were defined in the ICR mice and their changes were observed over the exposure of various ELF-MFs. Our data show that the onset times of stop rearing and tonic-clonic seizure in the 4 Hz MF exposure group are significantly different from those of the sham group. Bioelectromagnetics 25:245,250, 2004. © 2004 Wiley-Liss, Inc. [source] PRECLINICAL STUDY: Stimulation of 5-HT1B receptors enhances cocaine reinforcement yet reduces cocaine-seeking behaviorADDICTION BIOLOGY, Issue 4 2009Nathan S. Pentkowski ABSTRACT Paradoxically, stimulation of 5-HT1B receptors (5-HT1BRs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT1BR agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3,10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0,1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT1BRs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT1BRs may be a novel target for developing medications for cocaine dependence. [source] Low dose cocaine self-administration transiently increases but high dose cocaine persistently decreases brain reward function in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Paul J. Kenny Abstract This study investigated the effects of self-administered cocaine on brain reward function, measured by intracranial self-stimulation (ICSS) reward thresholds in rats. Self-administration of 10 and 20 cocaine injections (0.25 mg per injection, equivalent to 4.94 ± 0.23 and 9.88 ± 0.46 mg/kg, self-administered over 40 ± 6.9 and 99 ± 11.9 min, respectively) lowered reward thresholds 15 min later, indicating a facilitation of rewarding ICSS, but had no effect at 2, 24 or 48 h after administration. Thus, self-administration of low cocaine doses did not cause persistent changes in brain reward function. Forty cocaine injections (19.64 ± 0.94 mg/kg; self-administered over 185 ± 10.9 min) also transiently lowered reward thresholds 15 min later, while significant threshold current elevations were observed at 2 and 24 h after administration, indicating persistent withdrawal-like reward deficits. Finally, 80 cocaine injections (39.53 ± 1.84 mg/kg, self-administered over 376 ± 19.9 min) significantly elevated thresholds 2 and 48 h after self-administration, but not at 24 h. Threshold currents also tended to be elevated 15 min after self-administration. Overall, these data suggest that as the amount of self-administered cocaine increases the motivation to consume further cocaine may be shifted, from obtaining the rewarding actions of cocaine to avoidance and alleviation of a cocaine-induced negative affective state. [source] | ||||||||||