Ibogaine attenuates morphine-induced conditioned place preference.

Ibogaine, a putative anticraving drug in humans, reduces the ability of a single injection of morphine to produce a place preference in rats (Rattus norvegicus). The attenuation of morphine's effect is seen even if ibogaine is administered 24 hr before the opiate. However, after the 4th morphine conditioning trial, ibogaine no longer modified morphine reward. Ibogaine alone is neither reinforcing nor aversive, and ibogaine does not affect place aversions produced by naloxone or lithium chloride. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-Amphetamine and ethanol on a measure of behavioral inhibition in rats.

This study was designed to develop a version of the stop task, a putative measure of behavioral inhibition, for use in rats and to assess the effects of d-amphetamine (AMP) and alcohol (ALC). The stop task provides a quantitative index of the ability to inhibit a response that has been initiated. Rats (N?=?11) were tested after intraperitoneal injections of AMP (0.125, 0.25, 0.5, 1.0 mg/kg) and ALC (250, 500, 750 mg/kg). AMP improved the ability to inhibit responses only in rats with relatively poor inhibitory performance at baseline. ALC impaired inhibition at doses that did not affect simple reaction time. The results support the sensitivity, reliability, and validity of the procedure as a measure of behavioral inhibition in rats and are highly concordant with a parallel study conducted with humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-Amphetamine and ethanol on a measure of behavioral inhibition in humans.

Little is known about the acute effects of psychoactive drugs on impulsivity and decision making in humans. This study examined the effects of d-amphetamine (AMP; 10 and 20 mg; N?=?20) and ethanol (EtOH; 0.2, 0.4, and 0.8 g/kg; N?=?17) on the stop task, a putative measure of behavioral inhibition and impulsivity in healthy human volunteers. The stop task provides a measure of the reaction time (RT) needed to inhibit a response (Stop RT [SRT]), relative to the time taken to execute a simple response (Go RT [GRT]). Healthy volunteers performed the stop task before and after receiving one of the drugs. AMP decreased SRT–that is, improved inhibition–only in participants with slow baseline SRTs. EtOH increased SRTs–that is, impaired inhibition–at doses that did not affect GRTs. These results suggest that AMP and EtOH have specific and distinctive effects on the ability to inhibit responses. Impairment in the ability to inhibit responses is thought to reflect a certain form of impulsivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice

Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylphenidate. Several lines of evidence have suggested that cocaine blockade of the dopamine transporter (DAT), perhaps with additional contributions from serotonin transporter (5-HTT) recognition, was key to its rewarding actions. We now report that knockout mice without DAT and mice without 5-HTT establish cocaine-conditioned place preferences. Each strain displays cocaine-conditioned place preference in this major mouse model for assessing drug reward, while methylphenidate-conditioned place preference is also maintained in DAT knockout mice. These results have substantial implications for understanding cocaine actions and for strategies to produce anticocaine medications.     

Elevated levels of impulsivity and reduced place conditioning with d-amphetamine: Two behavioral features of adolescence in mice.

Human adolescents may have experience with easily available psychoactive drugs. Impulsivity and/or peculiarities in reward systems may play a role. These variables were studied in adolescent (Postnatal Day [PND] 30-49) and adult (PND > 60) CD-1 mice. In Experiment 1 (impulsivity), food-restricted mice were tested in operant chambers with 2 nose-poking holes that delivered 1 food pellet immediately or 5 pellets after a delay, respectively. Delay length was increased over days (0-100 sec). Adolescent mice showed a shift to the left in the intolerance-delay curve, as well as enhanced demanding when nose-poking was not reinforced. In Experiment 2 (place conditioning with d-amphetamine at 0.0, 1.0, 2.0, 3.3, or 5.0 mg/kg for 3 days), adolescent mice showed no reliable evidence of place conditioning when compared with adults. Hence, 2 main features of adolescence were elevated impulsivity and restlessness, and low (or absent) rewarding efficacy of amphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminative Stimulus and Self-Reported Effects of Methylphenidate, d-Amphetamine, and Triazolam in Methylphenidate-Trained Humans.

Asymmetrical generalization between drugs on drug-discrimination procedures has been demonstrated for sedative and stimulant drugs in animals and to some extent with sedative drugs in humans. The aim of this experiment was to examine the discriminative-stimulus effects of d-amphetamine in methylphenidate-trained humans. A previous study demonstrated that methylphenidate substitutes for d-amphetamine in d-amphetamine-trained humans. Six healthy human participants first learned to discriminate 30 mg oral methylphenidate. Doses of oral methylphenidate, d-amphetamine, triazolam, and placebo were then tested to determine whether they share discriminative-stimulus and self-reported effects with 30 mg methylphenidate. Methylphenidate and d-amphetamine dose-dependently increased methylphenidate-appropriate responding and produced prototypical stimulant-like effects. Triazolam produced low levels of methylphenidate-appropriate responding and prototypical sedative-like effects. The results of this experiment are concordant with previous studies and suggest that the behavioral effects of oral methylphenidate and d-amphetamine overlap extensively and that the discriminative-stimulus effects of methylphenidate and d-amphetamine are symmetrical. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Baclofen facilitates the extinction of methamphetamine-induced conditioned place preference in rats.

The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABAB receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six-day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2 mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABAB receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Prefrontal cortex lesions differentially disrupt cocaine-reinforced conditioned place preference but not conditioned taste aversion.

Male rats were anesthetized, and 1 of 3 subfields (medial, orbital, or precentral) of the prefrontal cortex (mesocortical dopaminergic [DA] target regions) was removed by aspiration, or no brain injury was done (sham Ss). In 4 experiments, Ss were tested on conditioned place preference, conditioned taste aversion (saccharin conditioned stimulus [CS], cocaine [CE] unconditioned stimulus [UCS]), general activity in the running wheel and open field, and food-reinforced spatial alternation in the T-maze. Results show that sham Ss showed a CE-induced place preference, medial frontal lesion Ss showed a CE-induced place aversion, and other Ss showed neither. All Ss showed a conditioned taste aversion of equal magnitude, and there were no lesion-induced differences in activity in either the running wheel or the open field. Medial frontal Ss were impaired relative to the precentral and sham Ss on learning to alternate choices in the T-maze, but orbital frontal Ss' performance was not different from that of any other group. Results indicate that mesocortical DA projection regions are involved with mediating the reinforcing properties of CE, and there is a separate system mediating the aversive properties of CE. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment with a serotonin-depleting regimen of MDMA prevents conditioned place preference to sex in male rats.

Among young adults, 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular drug of abuse, and anecdotal evidence indicates that repeated use of MDMA may result in impairments in sexual function and decreased sex drive in human users. There has been little investigation of the effects of MDMA on sexual function in rodents. In the present study, the authors determined that in male rats (Rattus novegicus) tested in a sexually na?ve or a sexually experienced state, administration of a serotonin (5-HT)-depleting regimen of MDMA did not produce a change in mount, intromission, and ejaculation latency or in mount and intromission frequency compared with such latency and frequency in vehicle-treated control rats. In contrast to vehicle-treated rats, MDMA-treated rats did not form a conditioned place preference (CPP) to sex. Failure of MDMA-treated rats to form CPP to sex may be due to MDMA-induced impairments in circuits mediating sexual reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttrial d-amphetamine sulfate and one-trial learning in mice.

Conducted 3 experiments with a total of 216 male albino LACA mice to investigate the effect of dextroamphetamine sulfate on memory in such a way that (a) state-dependency learning effects were excluded, (b) the time of learning was known rather precisely, (c) the drug might be introduced rapidly after the learning trial if recovered, and (d) no previous learning experience or drug effects would be present to confound the interpretation of results. Results show that amphetamine (2 mg/Kg, iv) immediately after footshock on a 1-trial passive avoidance learning task impaired performance in retention tests 24 and 96 hrs later. When the injection was delayed by as little as 90 sec, no such impairment was seen. A similar injection immediately after the learning trial of a water-rewarded 1-trial appetitive task had no discernible effect on performance in retention trials 24 hrs and 6 wks later. It is argued that the effects of the amphetamines on learning behavior depend on whether reward or punishment is involved and, further, that all such effects could be accounted for in terms of the drugs' influence on memory mechanisms. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blockade of morphine- and amphetamine-induced conditioned place preference in the rat by riluzole

Three cases of isolated one-and-a-half syndrome with facial nerve palsy related to infarction are presented. Magnetic resonance imaging in cases 1 and 2 was unremarkable, whereas magnetic resonance angiography demonstrated pathophysiologically significant vertebral basilar disease. Case 3 is unique due to its association with giant cell arteritis. Ipsilateral adduction improved to a greater extent than abduction in each case, perhaps providing insight into the exact localization of these lesions or selective vulnerability of the ocular motor structures within the pons. This combination of clinical findings, termed the 8-1/2 syndrome (cranial nerve 7 + 1-1/2), allows precise localization, and magnetic resonance angiography appears to be the imaging study of choice.     

The NMDA receptor antagonist MK-801 elicits conditioned place preference in rats

(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate, (MK-801) a potent noncompetitive antagonist of central NMDA receptors, has been hypothesized to have rewarding properties indicative of abuse potential. To test this hypothesis, the effects of MK-801 on the acquisition of a conditioned place preference and on locomotor activity were assessed and compared with d-amphetamine. Both MK-801 (0.03 and 0.1 mg/kg, SC) and d-amphetamine (1.0 mg/kg, SC) administration resulted in the acquisition of a conditioned place preference. However, while both amphetamine and the higher dose of MK-801 produced a behavioral activation during the training period the lower dose of MK-801 did not. These results suggest that MK-801, at doses that produce behavioral activation and below, is rewarding and therefore may have abuse potential.     

Differential effects of 7-OH-DPAT on amphetamine-induced stereotypy and conditioned place preference

Cost-effectiveness and cost per successful treatment has been evaluated in 186 outpatients randomised to treat moderate to severe migraine attacks either with subcutaneous sumatriptan 6 mg (n = 97) or with their current therapy (n = 89) during an open, multicentre study of 3 months. Within 2 hours, headache severity decreased to none/mild in 86% of all attacks in the sumatriptan group (STG) compared to 25% in the customary group (CTG). Migraine was alleviated earlier in the STG than in the CTG (median 3.78 vs. 13.39 hours, p < 0.0001). The direct and total cost of treatment was 133 and 2012 BF, respectively, in the CTG and 1400 and 2522 BF, respectively, in the STG. Measuring the effectiveness of earlier pain relief with sumatriptan, the incremental cost-effective ratios for direct and total cost were 132 and 53 BF per hour of relieved pain, respectively. For this price, significantly more sumatriptan patients improved their quality of life by more than 20% (61.6 vs. 20.6% patients, p < 0.001) and less sumatriptan patient consulted a medical professional (11.3 vs. 29.2% patients, p < 0.01), used less medication for adverse events (6.2 vs. 22.5%, p < 0.001) and suffered less from associated migraine symptoms. The median number of hours of diminished work-efficiency (3 vs. 7 hours, p < 0.01) or of suspension of non-professional activity (10 vs. 24 hours, p < 0.001) was also significantly lower in the STG. The total cost per successfully treated patient was lower in the STG. Sumatriptan is more effective, provides a better quality of life, reduces health care resource utilisation, and improves work productivity as compared to the CTG, thereby resulting in a favourable cost-effectiveness ratio.     

The development of a conditioned place preference to morphine: Effects of lesions of various CNS sites.

This study examined the neural substrates underlying the development of a conditioned place preference (CPP) to morphine (2 mg/kg?×?3 pairings) by testing whether lesions of 7 different neural sites block a morphine-induced CPP. Lesions of the pedunculopontine tegmental nucleus (PPTg), the periaqueductal gray (PAG), or the fornix reduced the preference for a morphine-paired compartment. When they were retested following morphine administration, fornix- or PAG-lesioned animals exhibited a CPP indicating that lesions did not block morphine-induced reward or the ability to associate this effect with salient environmental cues. PPTg-lesioned animals did not express a CPP during state-dependent testing, suggesting that the lesions may attenuate the rewarding effect of the drug. Lesions of the mesolimbic dopamine system, the ventral pallidum, the lateral nucleus of the amygdala, or the caudate putamen had no effect on a morphine-induced CPP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults.

Adolescence is a transitional period during development that is associated with a greater likelihood of addiction to drugs than any other age. One possibility for this observation is that learned associations between the rewarding experience of drugs and drug-related cues may produce greater motivational salience, and thus are more difficult to extinguish. Using an unbiased place-conditioning paradigm with two doses of cocaine (10 mg/kg or 20 mg/kg), the authors show here that adolescents require 75 ± 17% more extinction trials than adults to extinguish cocaine place-preferences. Furthermore, once extinguished, adolescents display a greater preference for a previously cocaine-paired environment upon drug-primed reinstatement compared with adults. These results suggest that adolescent vulnerability to addiction involves robust memories for drug-associated cues that are difficult to extinguish. Therefore, drug-addicted adolescents may have a higher risk of relapse than adults, leading to greater prevalence of addiction in this population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphine, MDMA, MDA, and nexus produce a conditioned place preference in newly hatched chickens.

The current study was undertaken to determine whether morphine and three amphetamine-related designer drugs would produce a conditioned place preference in newly hatched chickens (Gallus gallus). MDMA (3,4-methylenedioxymethamphetamine) and Nexus (4-bromo-2,5-dimethoxyphenethylamine) produced a place preference at intermediate doses; MDA (3,4-methylenedioxyamphetamine) produced a place preference only at the highest dose; and morphine produced a place preference only at the lowest dose tested. A second experiment was then conducted in which the same drugs were administered outside the context of the place preference apparatus. With the exception of Nexus, none of the drugs caused in a change in preference for the initially preferred side, suggesting that the place preference seen with Nexus in Experiment 1 was of a dissociative nature (i.e., not a true conditioned place preference). Results suggest that the newly hatched chicken may be an inexpensive, alternative species for studying drug-conditioned place preferences, but the results also emphasize the importance of conducting the proper control experiments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug-induced hypothermia and conditioned place aversion.

Examined the relationship between ethanol's thermal and motivational effects in a place conditioning task. In 3 experiments, male albino rats were exposed to a differential conditioning procedure that paired a distinctive tactile stimulus with ethanol (1.2 or 1.8 g/kg) or lithium chloride (3 meq/kg); a different stimulus was paired with saline. Different groups were exposed to ambient temperatures (Ta) of 5°, 21°, or 32°C during each 60-min conditioning trial. Both ethanol and lithium chloride produced hypothermia and conditioned place aversion in rats conditioned at normal Ta. Exposure to high Ta reduced drug-induced hypothermia, increased activity, and decreased conditioned place aversion. Exposure to low Ta did not enhance drug-induced hypothermia or change conditioned place aversion. In general, these findings support the suggestion that the hedonic effects of ethanol and lithium chloride interact with their thermal effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of ejaculation induced by 8-OH-DPAT does not produce conditioned place preference in male rats.

The serotonin 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) produces a drastic facilitation of ejaculation characterized by a significant reduction in the number of pre-ejaculatory intromissions and a shortening of ejaculation latency. In the present study, the authors evaluated whether this facilitation of ejaculation can induce a reward state assessed by conditioned place preference. Males treated with 0.1 or 1.0 mg/kg of 8-OH-DPAT showed a clear facilitation of ejaculation but did not develop conditioned place preference. These results clearly indicate that the pharmacological facilitation of ejaculation and the reduction of the number of intromissions does not necessarily make sex rewarding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphine-conditioned changes in locomotor activity: Role of the conditioned stimulus.

When a multisensory environment was reliably paired with morphine (2 mg/kg) in rats, that environment, in a drug-free test, evoked a hyperactive conditioned response (CR). When an olfactory cue (banana odor) was the only stimulus element reliably paired with morphine, it also elicited a hyperactive CR. However, a gustatory cue (saccharin solution) evoked a hypoactive CR. This taste-elicited decrease in activity was dose dependent; morphine at 2 and 4 mg/kg conditioned hypoactivity, whereas a higher dose (8 mg/kg) did not. A robust conditioned saccharin aversion occurred only at the highest dose of morphine, suggesting disassociation between the hypoactive CR and taste aversion. A taste cue present during context conditioning also prevented either acquisition or expression of the hyperactive CR to the context. The modality of the conditioned stimulus is a critical determinant of the form of the CR in a morphine locomotor conditioning paradigm. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The place preference task: A new tool for studying the relation between behavior and place cell activity in rats.

This study describes a task that combines random searching with goal directed navigation. The testing was conducted on a circular elevated open field (80 cm in diameter), with an unmarked target area (20 cm in diameter) in the center of 1 of the 4 quadrants. Whenever the rat entered the target area, the computerized tracking system released a pellet to a random point on the open field. Rats were able to learn the task under light and in total darkness, and on a stable or a rotating arena. Visual information was important in light, but idiothetic information became crucial in darkness. Learning of a new position was quicker under light than in total darkness on a rotating arena. The place preference task should make it possible to study place cells (PCs) when the rats use an allothetic (room frame) or idiothetic (arena frame) representation of space and to compare the behavioral response with the PCs' activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)