The H(3) antagonist thioperamide reveals conditioned preference for a context associated with an inactive small dose of cocaine in C57BL/6J mice

in Behavioural Brain Research (2005), 160(1), 161-168

The histaminergic system has been speculated to be involved in the inhibitory control of drug reward, H-1 and H-2 antagonists having been found to potentiate conditioned place preference induced by ... [more ▼]

The histaminergic system has been speculated to be involved in the inhibitory control of drug reward, H-1 and H-2 antagonists having been found to potentiate conditioned place preference induced by morphine or cocaine. In contrast, the role of H-3 receptors in cocaine-induced place preference is still unknown. The present study tested the effects of thioperamide (0, 10 and 20 mg/kg, i.p.), an H-3 autoreceptor antagonist, on the development of a conditioned place preference induced by cocaine (0, 2 and 8 mg/kg, i.p.) in C57BL/6J mice. Thioperamide was injected 10 min before each cocaine-pairing session. The activity scores recorded on the first cocaine-pairing session were also used to test the effects of thioperamide on cocaine-induced locomotor activity. Thioperamide alone had no reinforcing effects and did not affect the conditioned place preference induced by 8 mg/kg cocaine. However, thioperamide dose-dependently revealed a conditioned place preference induced by 2 mg/kg cocaine, a dose that was inactive per se. Finally, thioperamide dose-dependently potentiated the stimulant effects of cocaine, in spite of its slight hypolocomotor effect when given alone. Our results strongly suggest that H3 antagonists potentiate the stimulant and reinforcing effects of cocaine in mice. © 2004 Elsevier B.V. All rights reserved. [less ▲]

Effects of central administration of naloxone during the extinction of appetitive sexual responses

in Behavioural Brain Research (2004), 153(2), 567-572

Several studies indicate that opioids are involved in the control of consummatory sexual behavior in male Japanese quail. Naloxone has been reported to increase copulatory responses. In the current study ... [more ▼]

Several studies indicate that opioids are involved in the control of consummatory sexual behavior in male Japanese quail. Naloxone has been reported to increase copulatory responses. In the current study, the effect of naloxone on appetitive sexual behaviors was assessed during extinction test trials. Naloxone was found to substantially reduce appetitive responding, suggesting that opioids differentially affect anticipatory and contact components of sexual behavior. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

The magnitude and the extinction duration of the cocaine-induced conditioned locomotion-activated response are related to the number of cocaine injections paired with the testing context in C57BL/6J mice

in Behavioural Brain Research (2003), 145(1-2), 113-123

Behavioural activation repeatedly induced by a stimulant in rodents can persist in the absence of the drug if the animals are tested in the context where the drug was previously given, a phenomenon often ... [more ▼]

Behavioural activation repeatedly induced by a stimulant in rodents can persist in the absence of the drug if the animals are tested in the context where the drug was previously given, a phenomenon often explained in terms of Pavlovian conditioning. The aim of this study was to verify whether the amplitude of the putative CR (the drug-like activity) increases with the number of the US-CS associations (the number of drug-context pairings), one of the most representative rules of Pavlovian conditioning. The effect of the number of trials on the speed of extinction was also considered. C57BL/6J mice received 3, 6 or 12 once-daily injections of either saline or 12 mg/kg (-)-cocaine hydrochloride (s.c.) in the same test context, a photocell activity-box in which they were tested for 60 min after every injection. Other groups received the same treatments outside of the test context (being placed in a novel cage tub after each injection). Twenty-four hours after the last treatment session, all mice were challenged with saline in the test context (test for conditioned activity), extinction sessions taking place on the three subsequent days. Sensitisation to the locomotor-activating effect of cocaine developed only amongst the animals injected 6 or 12 times, the magnitude of the last sensitised response being comparable for these two injections regimen. On saline challenge, only the animals that had received 6 or 12 cocaine injections showed significant conditioned activity (CR), with the greatest response occurring following 12 injections. The 6-trial group reached the level of non-significance after fewer extinction sessions than the 12-trial group; however, the rates of extinction did not differ (comparable regression coefficients and quasi-parallel curves). These results suggest that the amplitude of the CR (cocaine-like stimulation after saline), and perhaps less convincingly the duration of extinction, are functions of the number of the US-CS (cocaine-context) pairings, supporting the Pavlovian nature of post-sensitisation placebo drug-like effects. (C) 2003 Elsevier Science B.V. All rights reserved. [less ▲]

Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice

in Behavioural Brain Research (2003), 142(1-2), 41-52

The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870 ... [more ▼]

The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870, their mutual combination, and the combination of the D4 agonist with representative compounds acting as agonist or antagonist on the D1, D2 and the D3 receptors. Memory consolidation was assessed in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the compounds being injected immediately after training (foot-shock) and performance measured 24h later. PD168,077 (0.5-10mg/kg) dose-dependently improved memory performance and L745,870 (0.05-5mg/kg) at doses lower than 1mg/kg increased and at doses higher than 1mg/kg impaired memory performance. PD168,077 did not affect the paradoxical promnesic effect of low doses (0.1-0.5mg/kg) of L745,870, but antagonised the memory-impairing effect induced by 5mg/kg L745,870. The D1 antagonist SCH23390 (0.025-0.05 mg/kg) and the D2 antagonist eticlopride (0.01-0.05 mg/kg) antagonised the promnesic effects of PD168,077, which attenuated the decreasing effect on memory consolidation of both D1 and D2 antagonists. Accordingly, the D1 agonist SKF38393 (5-20mg/kg) and the D2 agonist quinelorane (0.1-1 mg/kg) both synergistically magnified the memory-improving effects of the D4 agonist. The dopamine D3 antagonist U99194A (2.5-10mg/kg) did not affect the promnesic effects induced by the D4 agonist, which nevertheless abolished the U99194A-induced promnesic effects. Additionally, the amnesic effects produced by the D3 agonist 7-OH-DPAT (0.01-1 microg/kg) was attenuated by PD168,077. These results suggest a potential role of dopamine D4 receptors in memory consolidation, which would be similar to that of the D1 and D2 receptors and probably opposite to that of the D3 receptors. [less ▲]

Post-sensitisation conditioned hyperlocomotion induced by cocaine is augmented as a function of dose in C57BL/6J mice

in Behavioural Brain Research (2002), 132(2), 179-186

The study tested the possibility of a positive relationship between the dose of cocaine and the size of the placebo effect generated after contextual sensitisation to the behavioural effects of cocaine ... [more ▼]

The study tested the possibility of a positive relationship between the dose of cocaine and the size of the placebo effect generated after contextual sensitisation to the behavioural effects of cocaine. Male C57BL/6J mice were first injected (subcutaneous, s.c.) over seven successive daily sessions with saline or one of three doses of cocaine (2.5, 5 or 7.5 mg/kg), either in the test room or in the colony room (before being placed in a novel cage tub). On the test day, 24 h after chronic pre-treatment, mice from the four conditions were challenged under saline in the test room. Mice were video-recorded and their behaviours were scored using a time-sampling technique. A dose-dependent development of sensitisation was first generated. On the saline challenge test day, significant levels of placebo hyperlocomotion were obtained for mice previously given 5 and 7.5 mg/kg, but not 2.5 mg/kg cocaine, the effect being significantly greater in the mice pretreated with the highest dose than in those receiving the intermediate one, which exhibited a placebo effect that was greater than that of the mice pretreated with 2.5 mg/kg cocaine. Therefore, the magnitude of the placebo effect was a function of the intensity of the unconditioned stimulus (the dose used to generate sensitisation). Such results directly support the Pavlovian conditioning account of post-sensitisation placebo effects. [less ▲]

Functional Maturation of the Gabaergic Inhibition on Dopamine-Mediated Behaviours During the Neonatal Period in the Mouse

in Behavioural Brain Research (1989), 33(1), 83-95

Previous works have indicated that systemic injection of GABA-agonists depress motoric behaviours in neonatal murids, suggesting an early maturation of GABAergic inhibitory processes. In this paper, the ... [more ▼]

Previous works have indicated that systemic injection of GABA-agonists depress motoric behaviours in neonatal murids, suggesting an early maturation of GABAergic inhibitory processes. In this paper, the inhibitory effects of muscimol, a postsynaptic GABAA-agonist, on D-amphetamine-induced enhancement of locomotion, wall-climbing and head-raising were examined in neonatal 5-, 8- and 11-day-old mouse pups, using a direct observational procedure. The results show that muscimol can selectively attenuate high levels of locomotion, wall-climbing and head-raising produced by the indirect dopamine agonist in 8- as well as 11-day-old pups. However, while muscimol is able to moderate amphetamine-induced wall-climbing and head-rising in 5-day-old pups, no GABAergic inhibition was seen for locomotion at this age. Licking episodes elicited by amphetamine in 11-day-old pups can be magnified by muscimol if the dosage of the former is relatively too potent. It is suggested that the GABAergic inhibitory processes on dopaminergic functioning have reached good levels of functional maturation in the neonatal murid. [less ▲]