Characterization of the rapid-onset type of behavioral sensitization to amphetamine in mice: Role of drug-environment conditioning

A rapid-onset type of behavioral sensitization (ROBS) has been demonstrated in rats treated with a single 'priming' injection of amphetamine (AMP). in that species, however, this phenomenon was restricted to AMP-induced stereotyped behavior (SB), not occurring for the locomotor-stimulant effect (LSE) of AMP and not reflecting environment-specific sensitization. in the present study, the ROBS was characterized in the mouse. Mice received a single 'priming' intraperitoneal injection of 5.0 mg/kg AMP which was paired or not with environment. At different intervals (3, 4 or 5 h) subgroups were tested for AMP (1.5 or 5.0 mg/kg)-induced SB or AMP (1.5 mg/kg)-induced open-field LSE. Results showed that: (1) in the absence of drug-environment association, a priming injection of AMP increased the SB induced by a 1.5 mg/kg AMP challenge injection given 3 h (but not 4 or 5 h) later; (2) when the dose of AMP challenge injection was increased to 5.0 mg/kg, an enhancement of SB was verified at all the intervals tested (3, 4, and 5 h); (3) when animals were tested in an open field, the priming injection of AMP produced an increase in the LSE of a 1.5 mg/kg AMP challenge injection, given 4 h later; (4) drug-environment association increased both SB and locomotion after a saline challenge injection and potentiated the rapid-onset sensitization of both behaviors in AMP-challenged mice. Collectively, these results demonstrate that the ROBS phenomenon also occurs in mice, is extended to AMP-induced LSE, and is markedly potentiated by (but does not depend on) environmental conditioning.Universidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, BR-04023062 São Paulo, BrazilWeb of Scienc

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Effects of buspirone on an animal model of tardive dyskinesia

1. the effects of buspirone were studied on an animal model of tardive dyskinesia, i.e., the quantification of orofacial dyskinesia in rats repeatedly treated with reserpine.2. Rats were co-treated with saline [SAL] or buspirone [BUS] (3.0 mg/kg, i.p., twice daily) and vehicle [VEH] or reserpine [RES] (0.1 mg/kg, s.c., once every other day) for 19 days. On the day 20, the animals were observed for quantification of the behavioral parameters of orofacial dyskinesia: tongue protrusion and vacuous chewing movements frequencies and duration of twitching of the facial musculature.3. Rats of the SAL+RES group exhibited a significant increase in the three behavioral parameters of orofacial dyskinesia relative to the rats of the SAL+VEH group. However, animals of the BUS+RES group showed only an increased frequency of vacuous chewing movements when compared to animals of the SAL+VEH group. in addition, the duration of the facial twitching was significantly decreased in the BUS+RES group in relation to rats of the SAL+RES group. There were no significant differences in the orofacial parameters between the BUS+VEH and the SAL+VEH groups.4. Because it was also verified that chronic buspirone treatment was able to increase apomorphine-induced yawning behavior, the possibility is raised that buspirone attenuates reserpine-induced orofacial dyskinesia through the development of dopamine autoreceptor supersensitivity.Universidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, São Paulo, BrazilWeb of Scienc

One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. the present study was designed to examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience. (C) 2002 Elsevier Science Inc. All rights reserved.Universidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of Scienc