Dorsal hippocampus inhibition disrupts acquisition and expression, but not consolidation, of cocaine conditioned place preference.

Cocaine abusers may experience drug craving upon exposure to environmental contexts where cocaine was experienced. The dorsal hippocampus (DHC) is important for contextual conditioning, therefore the authors examined the specific role of the DHC in cocaine conditioned place preference (CPP). Muscimol was used to temporarily inhibit the DHC and was infused before conditioning sessions or tests for CPP to investigate acquisition and expression of cocaine CPP, respectively. To investigate consolidation, rats received intra-DHC muscimol either immediately or 6 hr after conditioning sessions. Inhibition of DHC, but not the overlying cortex, disrupted acquisition and expression of cocaine CPP. It is interesting to note that there was no effect of postconditioning DHC inhibition. The findings suggest that the DHC is important for both acquisition and recall, but not consolidation, of context-cocaine associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone facilitates extinction but does not affect acquisition or expression of ethanol-induced conditioned place preference.

Mice (DBA/2J) received a Pavlovian procedure in which a distinctive floor stimulus was paired 4 times with ethanol (2 g/kg). A different floor stimulus was paired with saline. Naloxone (0.0, 1.5, or 10.0 mg/kg, intraperitoneal) given before each ethanol trial did not interfere with acquisition of conditioned preference, although naloxone alone produced conditioned aversion. When naloxone (0.0, 0.15, 1.5, 3.0, or 10.0 mg/kg) was given for the first time during testing, mice showed conditioned preference during the first 10 min. However, preference subsequently decreased dose-dependently over time. Control studies eliminated alternative interpretations based on pharmacokinetics or presence of an aversive state. The overall pattern of results suggests that naloxone facilitated extinction of conditioned place preference and supports the hypothesis that ethanol-induced conditioned reinforcement is mediated by the endogenous opioid system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential involvement of enkephalins in analgesic tolerance, locomotor sensitization, and conditioned place preference induced by morphine.

In this study, the authors investigated the role of enkephalins in morphine-induced conditioned place preference, locomotor sensitization, and analgesic tolerance. Both preproenkephalin wild type (ppENK [+/+]) and knockout (ppENK [-/-]) mice showed similar preference for the morphine-paired chamber over the vehicle-paired chamber, indicating morphine induced comparable conditioned place preference in ppENK (+/+) and ppENK (-/-) mice. Sensitization developed to the motor stimulatory action of morphine after its repeated administration, but the magnitude of this response was not altered in ppENK (-/-) mice. However, as shown previously, ppENK (-/-) mice displayed blunted morphine analgesic tolerance. Taken together, the results suggest that enkephalins may be important for the development of analgesic tolerance but not for conditioned place preference or behavioral sensitization induced by morphine. (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)     

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)     

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.     

Attenuation of ethanol-induced conditioned taste aversion in mice sensitized to the locomotor stimulant effects of ethanol.

This study examined the effect of repeated ethanol (EtOH) injections that induced behavioral sensitization on subsequent acquisition of EtOH- and lithium chloride (LiCl)-induced conditioned taste aversion (CTA). CTA acquisition was assessed in independent groups of EtOH-sensitized and nonsensitized genetically heterogeneous female mice after injections of saline; 1, 2, or 4 g/kg EtOH; or 2 or 4 mEq/kg LiCl. Saline and 1 g/kg EtOH did not induce CTA. Four g/kg EtOH and 4 mEq/kg LiCl induced similar levels of CTA in EtOH-sensitized and nonsensitized groups. CTA induced by 2 g/kg EtOH and 2 mEq/kg LiCl was attenuated in EtOH-sensitized mice compared with nonsensitized counterparts. Thus, a sensitizing regimen of EtOH preexposure resulted in both a decrease in EtOH and LiCl aversion and an increase in EtOH locomotor sensitivity; such changes could ultimately contribute to enhanced EtOH intake and potentially to EtOH abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transient inactivation of the ventral tegmental area selectively disrupts the expression of conditioned place preference for pup- but not cocaine-paired contexts.

The ventral tegmental area (VTA) plays a critical role in motivated behavior. However, it remains unclear whether intact VTA function is necessary for motivated behavior to seek contexts repeatedly paired with natural stimuli and/or pharmacological stimuli. In the present study, conditioned place preference (CPP) was induced with highly salient natural or drug stimuli attributed with strong incentive–motivational value in each of 2 female models: Postpartum females were conditioned to associate one unique context in the CPP apparatus with young offspring (pups) and a second context with a neutral stimulus, and virgin females were conditioned to associate unique contexts with cocaine (5 mg/kg ip) and saline injections. Immediately before CPP testing, each female received a microinfusion of bupivacaine bilaterally into the VTA to transiently inactivate the region; subjects were also tested after saline microinfusion into the VTA. Postpartum females’ preference for the pup-paired context was abolished by VTA inactivation but was restored to high control levels after saline microinfusion. In separate tests, VTA inactivation also reduced motivated pup licking and pup retrieval in postpartum females, suggesting that intact VTA function is required for the expression of both pup CPP and motivated pup-directed behaviors. Cocaine CPP remained unaffected by VTA inactivation. Locomotion was not affected by VTA microinfusions but was severely impaired by bupivacaine microinfusions into the substantia nigra. We concluded that the VTA is differentially involved in the expression of conditioned preference for contexts paired with pups, a salient natural stimulus, and contexts paired with cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy impairs the memory of recently, but not remotely, acquired trace eyeblink conditioned responses.

New Zealand male rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink conditioning paradigm using a 250-ms tone conditioned stimulus, a 100-ms airpuff unconditioned stimulus, and a 500-ms trace interval. Rabbits received bilateral hippocampal aspirations either 1 day or 1 month after learning. Controls consisted of time-matched sham-operated and neocortical aspirated rabbits. When retested on the trace paradigm, rabbits with hippocampal aspirations 1 day after learning were significantly and substantially impaired in the retention of trace conditioned responses. In contrast, rabbits that received hippocampal aspirations 1 month after training retained trace conditioned responses at a level comparable to that of the controls. Moreover, hippocampectomy had no effect on the retention of delay eyeblink conditioning. Thus, the hippocampus appears to be necessary for the retention of recently acquired, but not remotely acquired, trace conditioned responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone, but not flupenthixol, disrupts the development of conditioned ejaculatory preference in the male rat.

Male rats display a conditioned preference to ejaculate with a female bearing an odor paired previously with copulation to ejaculation. The present study examined the role of endogenous opioid and dopamine systems in this preference. Male rats received saline, the opioid receptor antagonist naloxone, or the dopamine receptor antagonist flupenthixol prior to 10 conditioning trials in a pacing chamber with an almond-scented female. On the final test, all males were injected with saline and given access to 2 females, 1 scented and the other unscented, in an open field. Only males injected with naloxone during training failed to manifest a conditioned ejaculatory preference. These findings suggest that activation of opioid, but not dopamine, systems during sexual interaction are necessary for conditioned ejaculatory preference in male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of the naltrexone implant on rodent social interactions and cocaine-induced conditioned place preference

It is well known that excessive thyroid hormone in the body is associated with bone loss. However, the mechanism by which thyroid hormone affects bone turnover remains unclear. It has been shown that it stimulates osteoclastic bone resorption indirectly via unknown mediators secreted by osteoblasts. To determine if interleukin-6 (IL-6) or interleukin-11 (IL-11) could be the mediator(s) of thyroid hormone-induced bone loss, we studied the effects of 3,5,3'-tri-iodothyronine (T3) on basal and interleukin-1 (IL-1)-stimulated IL-6/IL-11 production in primary cultured human bone marrow stromal cells. T3 at 10(-12)-10(-8) M concentration significantly increased basal IL-6 production in a dose-dependent manner. It also had an additive effect on IL-1-stimulated IL-6 production, but failed to elicit a detectable effect on basal or IL-1-stimulated IL-11 production. Treatment with 17beta-estradiol (10(-8) M) did not affect the action of T3 on IL-6/IL-11 production. These results suggest that thyroid hormone may stimulate bone resorption by increasing basal and IL-1-induced IL-6 production from osteoblast-lineage cells, and these effects are independent of estrogen status.     

Delta9-tetrahydrocannabinol, but not the endogenous cannabinoid receptor ligand anandamide, produces conditioned place avoidance

Although exogenous cannabinoid ligands such as delta9-tetrahydrocannabinol (THC) have been implicated in reward-related learning and aversion, the hedonic effects of the endogenous cannabinoid agonist anandamide (arachidonylethanolamide) have never been assessed. Thus, the effects of anandamide were tested in a place conditioning task. Male Wistar rats received THC (0.0-8.0 mg/kg) or anandamide (0.0-16.0 mg/kg) during conditioning sessions. The half-life of anandamide was increased by pretreatment with the protease inhibitor phenylmethylsulfonyl fluoride (2.0 mg/kg). A significant place aversion was found at the 1.0 and 1.5 mg/kg doses of THC. No significant place conditioning effects were found with anandamide. Locomotor activity during conditioning was significantly decreased by the 1.0, 1.5, 2.0 and 4.0 mg/kg doses of THC as well as the 8.0 and 16.0 mg/kg doses of anandamide. These results fail to implicate the endogenous cannabinoid anandamide in reward-related learning or aversion.     

The development of a conditioned place preference to morphine: effects of microinjections into various CNS sites

This study examined the neural substrates underlying the development of a conditioned place preference (CPP) to morphine (2 mg/kg x 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.     

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)     

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)     

Hunger enhances the expression of calorie- but not taste-mediated conditioned flavor preferences.

Compared ethanol-mediated flavor preferences to preferences mediated by saccharin, which is sweet but noncaloric, and sucrose, which is both sweet and caloric in 4 experiments, using 74 Long-Evans rats. Ss learned to associate grape or orange flavor conditioned stimulus/stimuli (CS) with (1) ethanol or saccharin solution or (2) either the other unconditioned stimulus/stimuli (UCS) or plain tap water. They were then given 2-bottle choice tests between the flavor CSs apart from the UCSs. Flavors associated with 5% ethanol were preferred over saccharin-paired and water-paired flavors by sated Ss, and food deprivation during the choice test enhanced this preference. Flavors associated with 8% sucrose were preferred over water-paired flavors, and this preference was also enhanced by food deprivation. Flavors associated with 0.028% or 0.25% saccharin were preferred over flavors paired with water. In all cases, calorie-mediated preferences, at their highest levels, were stronger than taste-mediated preferences. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the medial preoptic area interfere with the display of a conditioned place preference for vaginocervical stimulation in rats.

The present study examined the effect of ibotenic acid lesions of the medial preoptic area (mPOA) on the expression of a conditioned place preference (CPP) for vaginocervical stimulation. Rats with bilateral lesions of the mPOA failed to display the CPP for vaginocervical stimulation shown by rats with sham or incomplete lesions. These findings provide additional support for the role of the mPOA in the neural circuitry underlying the reinforcing effects of female sexual behavior and raise the possibility that the altered pattern of approach and withdrawal behavior observed following lesions of the mPOA may be attributable in part to a diminution of the reinforcing effects of vaginocervical stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A morphine-paired environment alters c-Fos expression in the forebrain of rats displaying conditioned place preference or aversion.

The question of whether a common mechanism mediates both aversive and rewarding drug-paired cues is still unclear. In this study, we used a place preference conditioning paradigm to train rats to associate 1 chamber with morphine and the other chamber with saline. On the test day, rats were divided into those displaying conditioned place preferences (CPP) versus conditioned place aversion (CPA). After the test, all rats were killed and c-Fos immunocytochemistry was performed. For the control group, rats were treated with the same procedure except that the injections of morphine or saline had no association with the chambers. Compared with the control group, the CPP and CPA groups showed a significant increase of c-Fos expression in the dorsomedial striatum, central medial nucleus of the thalamus, and the basolateral amygdala. However, we saw no difference between CPP and CPA rats in any brain region examined. These results suggest that a morphine-paired environment can elicit neural activity in brain regions that are involved in emotional learning. Morphine-conditioned place preference and aversion may share a common neural circuitry elicited by a morphine-paired environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pro-Leu-Gly-NH? serves as a conditioned stimulus in the acquisition of conditioned tolerance.

The effect of Pro-Leu-Gly-NH? (MIF) on the acquisition of tolerance to morphine-induced antinociception and its efficacy as a cue predictive of morphine administration was examined. Daily administration of MIF prior to morphine injection did not attenuate the acquisition of tolerance to the antinociceptive properties of morphine, as measured by the latency to hindpaw lick in a hot-plate test of analgesia. When the animals were tested 72 hrs later without MIF pretreatment, they appeared to lose tolerance, as indicated by longer latencies to paw lick. These data suggest that in some situations MIF may interfere with the acquisition of tolerance by acting as a cue that reliably predicts the antinociceptive properties of morphine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)