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)     

Isradipine produces neither a conditioned place preference nor aversion

Isradipine (ISR) has been reported to block cocaine-induced conditioned place preference. Using this procedure, the pairing of this L-type calcium blocker, at doses of 2.5, 5.0 and 10 mg/kg, with a preferred (cue-distinct) environment was investigated. In a separate experiment, ISR injection (10 mg/kg) was paired with the less-preferred environment to determine whether ISR produces a place preference. Testing in the non-drugged state revealed that ISR conditioning failed to affect side preference in both experiments. The neutral affective properties of ISR may be relevant to the development of cocaine use/abuse treatment regimens.     

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)     

Taste avoidance, but not aversion, learning in rats lacking gustatory cortex.

Control rats rapidly learned to avoid drinking either a sucrose solution (Exp 1) or an NaCl solution (Exp 2) when the taste was paired with illness. These rats also produced aversive reactivity to each of these solutions in a taste reactivity test. Rats that lacked gustatory cortex (GC) learned to avoid drinking sucrose and NaCl, albeit at a slower rate than control rats. GC rats failed to display aversive reactivity to these tastes. The GC rats did show normal aversive reactivity to a strong quinine HCl solution during additional tests. It is suggested that the avoidance developed by GC rats did not entail a palatability shift of the conditional stimulus as it did in control rats. This altered learning strategy may account for the consistent learning deficits found in GC rats trained to avoid tastes. (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)     

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor?+?taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Area postrema lesions impair flavor-toxin aversion learning but not flavor-nutrient preference learning.

Rats with lesions of the area postrema. (APX) or sham lesions were trained to associate flavored solutions with positive or negative postingestive consequences. The APX rats were similar to controls in learning preferences for flavors paired with concurrent intragastric infusions of maltodextrin or corn oil and for a flavor paired with delayed maltodextrin infusions. In contrast, the APX rats displayed impaired aversion learning for flavors paired with toxic drug treatments (lithium chloride infusion or methylscopolamine injection). The aversion learning deficit ranged from mild to total, depending on training procedures. These findings confirm the important role of the area postrema in flavor-toxin learning but provide no evidence for its involvement in flavor-nutrient conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned flavor preference and aversion: Role of the lateral hypothalamus.

Food-restricted rats with ibotenic acid lesions of the lateral hypothalamus (LH) and sham controls were trained to associate flavored solutions with positive or negative postingestive consequences. The LH rats learned to prefer a flavor that was paired with concurrent intragastric infusions of maltodextrin. Unlike controls, the LH rats failed to learn a preference for a flavor paired with delayed maltodextrin infusions and showed an attenuated preference for a flavor paired with concurrent fat infusions. The LH rats did not differ from controls in learning to avoid flavors paired with concurrent or delayed infusions of lithium chloride. These data indicate that the LH is not essential for all types of flavor-postingestive consequence conditioning but is critical for learning to associate flavors with delayed nutrient feedback. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats.

In 2 experiments, the development of adjuvant arthritis (an experimental autoimmune disease) was inhibited by exposing rats to a flavored solution that had previously been paired with injections of cyclosporine (an immunodepressive drug) compared with rats with the same history but exposed to a flavored solution that had previously not been paired with drug injections. In contrast to earlier experiments on conditioned cyclophosphamide effects, rats did not avoid the taste that had previously been paired with drug administration. Thus, conditioned immunopharmacologic effects were not confounded with taste aversion. These observations are interpreted as reflecting an associative learning process that affected the development of an autoimmmune disease. (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)     

Transient sex differences in the between-sessions but not in the within-session memory underlying an active place avoidance task in weanling rats.

Spatial abilities were tested in male and female rats by training them to avoid an area in which there was a mild footshock while the arena rotated at 1 revolution/minute. The to-be-avoided area was stable in the coordinates of the room, so extramaze landmarks had to be used for accurate navigation, as the rotation made intramaze cues and substrate-based path integration useless for the avoidance. From Postnatal Day (PD) 19, rats were trained for 22 consecutive days. When the shock area was the same across sessions male rats reached optimal performance on PDs 23–24, 10 days before female rats, but when the location of the shock changed daily there were no sex differences. The results indicate that there are separate memory components underlying spatial competence: a within-session component that develops similarly in male and female rats and a between-sessions component that lasts at least 24 hr and appears earlier in male than in female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning of a flavor aversion in rats by amygdala kindling.

Rats received 30 stimulations and 30 sham stimulations (the lead was attached to the subjects but no current was delivered) to the left basolateral amygdala in a quasirandom sequence. Stimulations were preceded by the presentation of 1 flavored solution conditional stimulus (CS+); sham stimulations were preceded by the presentation of another flavored solution, CS-. As kindled motor seizures developed, the rats began to consume significantly less of the CS+ than the CS- Moreover, at the end of the experiment, the rats consumed significantly less of the CS+ than the CS- during a 20-min conditioned flavor preference test in which both solutions were available simultaneously. These findings confirm and extend the recent report that interictal changes in defensive behavior can be conditioned by amygdalar kindling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial location is critical for conditioning place preference with visual but not tactile stimuli.

The roles of visual, tactile, and spatial location cues were studied in 6 conditioned place preference (CPP) experiments with ethanol (2 g/kg) in mice (of the DBA/2J strain). Visual cues were effective conditioned stimuli (CSs) when consistently presented in the same spatial location, but not when the same cue was presented in two different locations during training. In contrast, tactile CSs were effective regardless of spatial location during training. Moreover, spatial location controlled CPP expression when visual cues were used but not when tactile cues were used. However, spatial location per se was not an effective CS. These studies suggest that CPP conditioned to tactile cues is mediated by brain systems different from those mediating CPP conditioned to visual-spatial cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous configuring in conditioned flavor aversion.

Four experiments with 202 rats investigated spontaneous configuring, using the conditioned flavor-aversion paradigm. In Exp I, extended training of a 2-flavor compound stimulus did not produce spontaneous differentiation of conditioned responding to that compound and its elements. In Exp II, it was found that extended nonreinforced exposure to a compound stimulus generated spontaneous element–compound differentiation when the elements were later conditioned. Ss that received extended preexposure to the compound showed less conditioned responding to the compound than to either of its elements. However, Ss that had not received preexposure to the compound showed greater conditioned responding to the compound than to either of its elements (summation). In Exp III, nonreinforced preexposure to a compound stimulus prior to minimal reinforced compound training produced spontaneous compound–element differentiation, but extended reinforced compound training eliminated that differentiation. In Exp IV, extended partial reinforcement training with a compound produced differentiation of the compound from its elements. Implications of these data for the mechanisms responsible for spontaneous configuring, and for the summation assumptions common to most learning theories, are discussed. (38 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Dorsal hippocampal lesions impair blocking but not latent inhibition of taste aversion learning in rats.

The aim of the present experiments was to study the effect of nonselective electrolytic lesions of the rat dorsal hippocampus on 2 learning phenomena: the L. J. Kamin (1969) blocking effect and latent inhibition of taste aversion learning. Bilateral dorsal hippocampal lesions selectively impaired blocking induced by 1 saccharin-lithium chloride pairing previous to 1 serial compound (saccharin–cider vinegar)–lithium pairing, but lesions had no effect on latent inhibition of a saline aversion, induced by 6 saline preexposures, in the same group of animals. Moreover, dorsal hippocampal lesions did not affect latent inhibition of saccharin-conditioned aversion induced by 1 or 6 preexposures. It is argued that blocking and latent inhibition of taste aversion learning do not share a common neural mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional decortication by cortical spreading depression does not prevent forced extinction of conditioned saccharin aversion in rats.

In 2 experiments conditioned taste aversion established in Druckrey hooded rats by association of saccharin drinking with subsequent lithium chloride intoxication decreased saccharin intake to 22% of normal consumption. Force-feeding saccharin to intact and functionally decorticate trained Ss returned saccharin consumption on the next day to 62% (n = 18) and 77% (n = 19), respectively. Overtrained conditioned saccharin aversion was affected by forced extinction in a similar way (saccharin intake increased from 28% to 50% and 63%, respectively). Intact-brain Ss refused to swallow saccharin during forced feeding, while functionally decorticate Ss showed no signs of aversion; extinction was almost equal in both cases. Application of lithium chloride after forced feeding of saccharin in functionally decorticate Ss neither prevented extinction of conditioned taste aversion nor reestablished the aversion habit extinguished earlier with intact brain. It is concluded that acquisition of the conditioned taste aversion requires cortical input to a short-term memory file, whereas decorticate extinction can be induced by subcortical gustatory processing analogous to the mechanism controlling feeding behavior during the preweaning period. (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)