Neurobiology of motivation: Double dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent animals.

Separate brain manipulations double dissociate 2 motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain-stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This 2nd dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clonidine antagonizes the aversive effects of opiate withdrawal and the rewarding effects of morphine only in opiate withdrawn rats.

The researchers asked whether clonidine, an α?-noradrenergic agonist, would block selectively the motivational effects of opiate withdrawal and whether clonidine's effects would respect the boundary between nondeprived and deprived motivational states. In a place conditioning paradigm, clonidine (0.05 mg/kg ip) blocked the rewarding effects of morphine in opiate-withdrawn rats (as well as the aversive properties of withdrawal itself), but did not affect morphine place preferences (2 and 20 mg/kg) in drug-naive rats. Furthermore, clonidine blocked the acquisition of morphine (15 mg/kg), but not LiCI (15 mg/kg), conditioned taste aversions in water-deprived rats. The results suggest that the motivational system activated in deprived animals includes dopaminergic and noradrenergic components that are in series with each other. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Yoked delivery of cocaine is aversive and protects against the motivation for drug in rats.

In Experiment 1, water-deprived rats had 5-min access to saccharin followed by active or yoked intravenous delivery of saline or cocaine (0.33 mg/infusion). Both cocaine groups avoided intake of the saccharin cue following saccharin–cocaine pairings; however, the rats in the yoked condition exhibited greater avoidance of the taste cue than did the actively administering rats. Experiment 2 evaluated subsequent self-administration behavior on fixed- and progressive-ratio schedules of reinforcement. The results showed that prior yoked exposure to cocaine reduced subsequent drug-taking behavior on a progressive-ratio but not on a fixed-ratio schedule. Finally, Experiment 3 used a choice test to determine the impact of yoked drug delivery on the relative preference for cocaine versus water. The results showed that rats with a history of self-administering cocaine preferred to perform operant behaviors on the side of the chamber previously paired with cocaine, whereas the rats with a history of yoked delivery of cocaine avoided this side. These data show that, in most rats, the unpredictable, uncontrollable delivery of cocaine protects against the subsequent motivation for cocaine through an aversive mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of N-methyl-D-aspartate receptor antagonists on discriminative stimulus effects of naloxone in morphine-dependent rats using the Y-maze drug discrimination paradigm

The present study assessed the ability of various site-selective N-methyl-D-aspartate (NMDA) receptor antagonists to affect the discriminative stimulus properties of naloxone in morphine-dependent rats. Adult male Wistar rats were trained to discriminate 0.1 mg/kg of s.c. naloxone from saline using a Y-maze shock-avoidance procedure. Naloxone-appropriate responding was exhibited as a function of naloxone dose (0.01-1.0 mg/kg, ED50 = 0.03 mg/kg) and was also observed when morphine treatment temporarily was discontinued (8-96 hr, peak at 24 hr). Discriminative stimulus effects of naloxone (0.1-3.0 mg/kg) were antagonized by morphine (10-100 mg/kg). Ligands of peripheral opioid receptors failed to either substitute for naloxone (methylnaloxone, 0.1-3.0 mg/kg) or attenuate naloxone's stimulus effects (loperamide, 1-30 mg/kg). In rats treated with the training dose of naloxone, administration of dizocilpine (0.03-0.3 mg/kg) and D-CPPene (1-10 mg/kg) decreased levels of naloxone-appropriate responding, whereas memantine (1-30 mg/kg), ACEA-1021 (10 and 50 mg/kg) and eliprodil (3-30 mg/kg) seemed to have little or no effects. Meanwhile, all NMDA receptor antagonists produced a decrease in the occurrence of two or more of the following opioid withdrawal signs: weight loss, forelimb tremor, ptosis, diarrhea and "wet-dog"-like shaking. Additionally, dizocilpine (0.1 mg/kg), D-CPPene (5.6 mg/kg) and ACEA-1021 (50 mg/kg) but not memantine (10 mg/kg) or eliprodil (30 mg/kg) significantly reduced the naloxone-appropriate escape area selection when administered during the period of suspended morphine treatment 24 hr after the last morphine injection. Thus, NMDA receptor antagonists appear to inhibit the discriminative stimulus effects of both naloxone-precipitated and spontaneous morphine withdrawal, and this ability depends on the type of antagonist applied.     

Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discrimination properties.

This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disinhibition and spontaneous recovery of response decrements produced by free reinforcement in rats.

Conducted 3 experiments with a total of 16 Holtzman albino and 48 hooded male rats. After the Ss had been trained to barpress on a variable interval schedule of reinforcement, response rates were reduced by the introduction either of extinction or of a response-independent (free) reinforcement schedule. Spontaneous recovery was consistently obtained in extinction, especially when session durations were long. Under free reinforcement conditions there was little sign of spontaneous recovery, even when with high reinforcement rates response reduction was almost as rapid as in extinction. In disinhibition tests the introduction of noise produced increased responding under free reinforcement conditions but not in extinction. Results are interpreted as demonstrating a dissociation between spontaneous recovery and disinhibition. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of conditional discriminations in hippocampal lesioned and decorticated rats: Evidence for learning that is separate from both simple classical conditioning and configural learning.

This study examined whether hippocampal or neocortical lesions would impair acquisition of a discrimination task using taste aversions. Male rats were injected with a drug 15 min before a flavored solution–LiCl pairing. On alternate days, vehicle injections preceded and followed access to the same flavored solution. Ss learned to consume significantly more of the flavored solution after vehicle injections than after drug injections. Ss with hippocampal lesions or neonatal decortication performed as well as controls. Ss with hippocampal lesions also learned a similar task in which visual and textural cues predicted whether access to a flavored solution would be followed by an injection of LiCl or vehicle. However, these hippocampal lesions did impair performance in the Morris water task. Occasion setting may involve a type of learning dissociated from both simple classical conditioning and configural learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context-specific morphine withdrawal in rats: Duration and effects of clonidine.

Rats previously injected with morphine in a particular environment (paired rats) emitted more withdrawal symptoms in that environment than did rats previously injected with morphine in another environment (unpaired rats) after both 1 day and 5 days of morphine abstinence. Thus, reexposure to an environment previously associated with morphine can elicit context-specific withdrawal even after several days of morphine abstinence. Clonidine (0.06 mg/kg) reduced most of the withdrawal symptoms seen 5 days after morphine abstinence in both the paired and unpaired rats. However, clonidine enhanced many of the withdrawal symptoms in both groups of rats during naltrexone-precipitated withdrawal 1 day after morphine abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contrast effects in paired comparisons: Evidence for both stimulus-based and response-based processes.

Participants made paired comparisons of square sizes, with blue squares presented on the left side of a computer screen and red squares on the right. Context was manipulated by varying the distributions of blue and red squares separately. In Exp 1, target squares from low-range distributions were judged larger than the same-size squares from high-range distributions. In Exp 2, ranges were equated but ranks manipulated between distributions, pairing bell with U-shaped and positively skewed with negatively skewed distributions. Results provided little support for a rank-dependent valuation model. Exp 3 used distributions that were designed to test between adaptation-level and response-equalization models. Both models received support, with response latencies constituting an important moderating variable. Response patterns for short latency participants were consistent with a stimulus-based adaptation-level process, and those for longer latency participants were consistent with a response-equalization process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response-based strengthening in task shifting: Evidence from shift effects produced by errors.

The hypothesis is introduced that 1 source of shift costs is the strengthening of task-related associations occurring whenever an overt response is produced. The authors tested this account by examining shift effects following errors and error compensation processes. The authors predicted that following a specific type of error, called task confusion, shift benefits instead of shift costs should result. A series of 3 experiments confirmed this prediction showing that task confusions produce shift benefits in subsequent trials (Experiment 1), even when the error is detected (Experiment 2). Moreover, only posterror processes that imply an error correction response produce shift costs (Experiment 3). These results additionally suggest that error detection cannot prevent errors from affecting subsequent performance. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discriminative properties

This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task.     

Specificity of empathy-induced helping: Evidence for altruistic motivation.

This experiment investigated altruistic vs. egoistic interpretations of the effect of empathic concern on helping. The empathy–altruism hypothesis posits that empathic concern arouses an altruistic motivation to relieve the distress of another person; the negative state relief interpretation proposes that the effect of empathic concern is mediated by sadness, which produces an egoistic motivation to reduce one's own unpleasant state. 96 male and 96 female Ss first listened with an imagine or observe set to another person's problem and then were given an opportunity to help that person with the same problem or with a different problem. Consistent with the empathy–altruism hypothesis, imagine-set Ss helped more often than did observe-set Ss for the same problem but not for a different one. In addition, only empathic concern associated with the specific problem related to helping. Although sadness was related to helping, it did not account for the effect of empathic concern. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynamic illusion effects in a reaching task: Evidence for separate visual representations in the planning and control of reaching.

The effects of an orientation illusion on perception and 2 different actions were investigated. An 8-cm?×?2-cm cylindrical bar was placed in front of participants at various orientations. A background grating was used to induce an orientation illusion. In a perception task, the illusion affected participants' ability to align the bar with their sagittal planes. In one reaching task, a similar effect of the illusion was found on the choice between 2 possible grasping postures. In a second reaching task involving a single grasping posture, the orientation illusion affected the orientation of the hand at the beginning of the reach but not near its end. The authors argue that reaching trajectories are planned and initiated through a context-dependent representation but are corrected on-line through a context-independent representation. The relation of this model to a more general dichotomy between perception and action is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of naloxone-precipitated withdrawal jumping by i.c.v. and i.t. administration of saline in morphine-dependent mice

In morphine-dependent mice, s.c. and i.t. administered naloxone produced withdrawal jumping (ED50 values were i.t. = s.c.) but i.c.v. administered naloxone failed to produce dose-dependent jumping. Peak times of jumping were earliest after i.t. administration of naloxone among the three administration routes. These results suggested that the spinal site was more sensitive to naloxone than the supraspinal site. Concomitant administration of naloxone i.c.v. and i.t. did not precipitate jumping. It was found that i.c.v. and i.t. injections of saline inhibited withdrawal jumping precipitated by s.c. administered naloxone and that the i.c.v. effect was more profound than the i.t. effect. I.c.v. injection of saline also delayed the peak time of withdrawal jumping precipitated by s.c. administered naloxone. These inhibitory effects of the injection procedures may explain the difficulty of i.c.v. administered naloxone and concomitant i.c.v. + i.t. administered naloxone to precipitate jumping, and may explain the difference in the ED50 values of naloxone and the time courses of jumping.     

Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze

PURPOSE: Endopyelotomy has become the initial treatment of choice for ureteropelvic junction obstruction. Debate persists regarding the preferred approach (percutaneous or ureteroscopic) and the need for preoperative stenting. We review our experience with ureteroscopic endopyelotomy without preoperative stenting. MATERIALS AND METHODS: We treated 21 patients a mean of 37 years old who had ureteropelvic junction obstruction with ureteroscopy and without preoperative stenting. Endoluminal ultrasound was performed in all cases for imaging the periureteral anatomy. A minimum of 1 year of followup is available in all cases. Success was defined as pain-free status with resolution of obstruction on diuretic renal scintigraphy. RESULTS: Success was achieved in 17 of 21 patients (81%). Complications included stent irritation, postoperative urinary tract infection and stent displacement requiring repositioning in 1 case each. Crossing vessels in 57% of the patients affected success (67 versus 100% in those with and without crossing vessels, respectively). No patient had significant hemorrhage. CONCLUSIONS: Ureteroscopic endopyelotomy without preoperative stenting is effective and safe for ureteropelvic junction obstruction.     

Limbic lesions and the energizing, aversive, and inhibitory effects of non-reward in rats.

Tested 30 male albino Wistar rats with bilateral lesions in the amygdala, septum, hippocampus, stria terminalis, and fornix on a multiple reinforcement schedule in which barpressing in one component was associated with VI reinforcement (S+) and the other with extinction (S–). Responses on a 2nd lever turned off S– for 5-sec periods during the extinction component. All groups, with the exception of Ss with amygdaloid lesions exhibited behavioral contrast. Ss with hippocampal or fornical lesions showed greater resistance to extinction. Response rates on the lever that turned off S– were higher after stria terminalis and septal lesions, whereas lower rates were obtained from Ss with amygdaloid lesions. It is concluded that amygdaloid lesions attenuate the energizing and aversive effects of nonreward, septal and stria terminalis lesions increase the aversive effects, and hippocampal and fornical lesions interfere with the inhibitory effects of nonreward. (French summary) (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of yohimbine and naloxone on copulatory behaviors of male rats.

Prior research has demonstrated that both yohimbine, an alpha?-adrenergic antagonist, and naloxone, an opiate antagonist, facilitate components of copulatory behaviors in nonstressed male rats. In the present experiments, it is demonstrated that these drugs differentially affect copulatory behaviors when the behavioral testing situation contained an aversive element. Male rats received an injection of lithium chloride (0.3 M, 20 ml/kg, ip) immediately after each encounter with an estrous female. Consequently, male copulatory behaviors gradually declined during successive test sessions. These male rats also received ip injections of either yohimbine (2 mg/kg/ml), naloxone (4 mg/kg/ml), or isotonic saline 20 min prior to each copulation test. Yohimbine-treated rats were more likely to copulate than control rats during both acquisition and extinction of lithium chloride-induced associative inhibition of copulatory behavior. Conversely, naloxone-treated rats were less likely to copulate than control rats during both acquisition and extinction. Data are consistent with the hypothesis that yohimbine increases sexual motivation in the male rat and limit the generality of the excitatory effects of naloxone on copulatory behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motivational and neuroanatomical specificity of hypodipsia for aversive solutions produced by medial preoptic injury to the rat.

In an experiment with a total of 28 Sprague-Dawley rats, bilateral medial preoptic lesions dramatically lowered the rejection threshold for quinine-adulterated water but not for food in 24-hr forced-choice tests. The detection threshold for quinine in a 2-bottle choice test, however, was unaffected by the medial preoptic lesion. Bilateral septal and lateral preoptic lesions had no effect on any quinine adulteration tests. The enhanced rejection of quinine-adulterated water in a forced-choice test by medial-preoptic-damaged Ss was also observed after 24 hrs of water deprivation. The plasma osmolality of medial preoptic Ss was significantly elevated above controls after 24 hrs of water deprivation. Findings suggest that a medial preoptic lesion produces a deficit in thirst-motivated behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-delay associations between drug states produced in rats by injecting two drugs in sequence.

Explored the Avfail effect (aversion failure) of the temporal relation of a pentobarbital (PB) injection paired with an Li injection on male Sprague-Dawley rats. In Exp I, 90 Ss were given Li and PB injections ip either simultaneously or with varying amounts of time in between injections. In Exps II and III, using 216 Ss, the length of delay and dosage amount were more varied. After forward pairings (PB before Li), with delays between the 2 injections varying among groups from 2.5 to 320 min, Avfail was obtained. There was little effect of the length of the forward delay, although the Avfail effect was slightly stronger at 30–40 min or so. When the 2 drugs were injected simultaneously or in a backward sequence, there was a weakening of the flavor aversion produced by PB; however, this is attributable to habituation to the drugs, not to Avfail. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)