Pedunculopontine tegmental nucleus lesions impair stimulus–reward learning in autoshaping and conditioned reinforcement paradigms.

The role of the pedunculopontine tegmental nucleus (PPTg) in stimulus–reward learning was assessed by testing the effects of PPTg lesions on performance in visual autoshaping and conditioned reinforcement (CRf) paradigms. Rats with PPTg lesions were unable to learn an association between a conditioned stimulus (CS) and a primary reward in either paradigm. In the autoshaping experiment, PPTg-lesioned rats approached the CS+ and CS– with equal frequency, and the latencies to respond to the two stimuli did not differ. PPTg lesions also disrupted discriminated approaches to an appetitive CS in the CRf paradigm and completely abolished the acquisition of responding with CRf. These data are discussed in the context of possible cognitive function of the PPTg, particularly in terms of lesion-induced disruptions of attentional processes that are mediated by the thalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-lasting increase in anxiety after electrolytic lesions of the pedunculopontine tegmental nucleus.

This study examined the effect of electrolytic lesions of the pedunculopontine tegmental nucleus (PPTg) on emotionality in rats. Rats with PPTg or sham lesions were tested in the elevated plus-maze, the social interaction test, the open-field test, and the conditioned fear paradigm. Histology showed that lesions were concentrated on the caudal half of the PPTg. In the plus-maze, behavioral scores were biased toward increased "anxiety" on the 1st testing day. Five consecutive exposures to the apparatus led to marked habituation in sham-lesioned but not in PPTg-lesioned rats. On the 5th day, most indexes of emotionality indicated elevated anxiety in PPTg-lesioned rats. Increased anxiety was also found in PPTg-lesioned rats in the social interaction test. In the conditioned fear paradigm, movement suppression during the postconditioned stimulus period was found in both groups on the 1st day of extinction but only in PPTg-lesioned rats on the 2nd extinction day, indicating extinction was slower in PPTg-lesioned rats. Lesions of the caudal PPTg appear to produce long-lasting anxiety in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the pedunculopontine tegmental nucleus increase sucrose consumption but do not affect discrimination or contrast effects.

Pedunculopontine tegmental nucleus (PPTg) lesions block place preferences to drugs or food only when animals are nondeprived. PPTg lesions also disrupt operant responding, but lesioned rats cannot discriminate active from inactive levers. It is not clear, therefore, whether PPTg lesions block reward or disrupt the ability to differentiate changes in reward magnitude. These hypotheses were tested by measuring sucrose consumption, choice, and contrast effects after PPTg lesions. Both sham and lesioned rats consumed greater amounts of a sucrose solution as the concentration and level of deprivation were increased. Given a choice between 2 solutions, all rats consumed more of the higher concentration. Both groups exhibited contrast effects when the concentration was shifted from 32% to 4% within a session. Somewhat surprisingly, lesions increased sucrose intake when rats were food-restricted. These results suggest that PPTg lesions do not disrupt primary motivation or the ability to evaluate and respond to changes in reward strength. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

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)     

Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine.

Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8–20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Operant and Pavlovian control of visual stimulus orienting and food-related behaviors in rats with lesions of the amygdala central nucleus.

The effects of superimposing operant reward and omission contingencies on 2 Pavlovian conditioned responses evoked by a visual conditioned stimulus paired with food were examined in rats with lesions of the amygdala central nucleus (CN). In sham-lesioned rats, the frequency of an orienting response, rearing, was increased by reward contingencies and decreased by omission contingencies, compared with yoked Pavlovian controls. In contrast, in CN-lesioned rats, rearing was not affected by either operant contingency and occurred at lower levels with Pavlovian procedures alone than in sham-lesioned rats. Nevertheless, CN-lesioned and sham-lesioned rats showed similar increases in the frequency of conditioned food-cup behavior with reward contingencies, similar decreases with omission contingencies, and similar levels of that response with Pavlovian procedures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adrenal responses to reinforcement and extinction: Role of expectancy versus instrumental responding.

Measured plasma corticosterone levels during operant conditioning to determine the effect of reinforced and nonreinforced responding (extinction) on adrenal activation; Ss were 44 male Long-Evans rats. The influence of instrumental responding was assessed by comparing trained Ss with yoked Ss that received a matched reward schedule in the absence of an operant task. Reinforcement sessions resulted in a significant decrease in adrenal secretion at 20 min but not at 5 min, whereas extinction caused a rapid increase in corticosterone levels at 5 min and an even greater elevation at 20 min. Comparison of the operant and yoked Ss showed that this effect of reinforcement and extinction was not dependent on instrumental responding, but rather on the receipt or withdrawal of the expected reward. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the pedunclopontine tegmental nucleus increase anxiety in rats

To test the hypothesis that the pedunclopontine tegmental nucleus (PPTg) plays a role in anxiety, rats with electrolytic lesions of the PPTg were tested in two animal models of anxiety, the elevated plus maze and the social interaction tests. Histological analysis showed that lesions were concentrated on the caudal half of the PPTg. In the elevated plus maze, traditional as well as 'risk assessment' measures indicated significantly increased anxiety in the PPTg-lesioned rats vs sham-operated controls. In the social interaction test, behavioural scores were biased towards elevated anxiety in the PPTg-lesioned rats but only the number of social sniffs reached significance. Our results confirm that electrolytic lesions of the caudal PPTg produce increased anxiety.     

Pharmacological and behavioral components of tolerance to LSD and mescaline in rats

A fixed-ratio schedule of water reinforcement (FR-10) was used to examine the relative contributions of pharmacological and behavioral mechanisms in the development of tolerance to the disruptive effects of LSD and mescaline in the rat. Rats treated daily with LSD or mescaline before operant testing developed tolerance to the impairement of responding, while rats treated daily after each session did not display tolerance when the drugs were administered before testing. These results indicate that behavioral compensatory mechanisms may be involved in the development of tolerance to the disruptive effects of LSD and mescaline on fixed-ratio (FR-10) performance.     

The effects of acquisition training schedule on extinction and reinstatement of cocaine self-administration in male rats.

Partial reinforcement is known to increase resistance to extinction (Rn) relative to training with continuous reinforcement. This phenomenon, referred to as the partial reinforcement extinction effect, is one of the most robust in learning and conditioning studies. Experiment 1 investigated manipulations known to affect the partial reinforcement extinction effect and determined their possible relevance for drug use patterns. Male rats received intravenous cocaine self-administration training under partial reinforcement (FR-10) training or continuous reinforcement (FR-1) conditions with either a low (0.25 mg/kg infusion) or a high cocaine dose (1.00 mg/kg infusion). Animals were placed on an extinction (recurrent nonreward) schedule for 10 days (1-hr sessions) prior to being tested for cue-induced reinstatement (single 2-hr session). Experiment 2 involved acquisition of cocaine self-administration under FR-1 conditions of short training (15 days) or extended training (30 days) with a low dose (0.25 mg/kg infusion) or a medium dose (0.50 mg/kg infusion) of cocaine reward prior to extinction or reinstatement. Experiment 1 showed that rats trained with FR-10-high dose outcomes exhibited greater Rn than the remaining groups. Additionally, FR-10-high dose and FR-10-low dose rats were more likely to return to active drug seeking during the reinstatement test. In Experiment 2, rats trained under FR-1-medium dose conditions were more persistent during extinction following short acquisition training than comparable rats experiencing extended acquisition training. The reinstatement test was conducted following extinction, in which it was observed that overtraining under FR-1-medium dose reward schedules resulted in a decrease in the tendency to return to active drug seeking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Appetitively motivated instrumental learning in SynGAP heterozygous knockout mice.

The synaptic Ras/Rap-GTPase-activating protein (SynGAP) regulates specific intracellular events following N-methyl-d-aspartate receptor (NMDAR) activation. Here, the impact of SynGAP heterozygous knockout (SG+/?) on NMDAR-dependent functions was assessed using different positive reinforcement schedules in instrumental conditioning. The knockout did not affect the temporal control of operant responding under a fixed interval (FI) schedule, but led to a putative enhancement in response vigor and/or disinhibition. When examined on differential reinforcement of low rates of response (DRL) schedules, SG+/? mice showed increased responding under DRL-4s and DRL-8s, without impairing the response efficiency (total rewards/total lever presses) because both rewarded and nonrewarded presses were elevated. Motivation was unaffected as evaluated using a progressive ratio (PR) schedule. Yet, SG+/? mice persisted in responding during extinction at the end of PR training, although an equivalent phenotype was not evident in extinction learning following FI-20s training. This extinction phenotype is therefore schedule-specific and cannot be generalized to Pavlovian conditioning. In conclusion, constitutive SynGAP reduction increases vigor in the execution of learned operant behavior without compromising its temporal control, yielding effects readily distinguishable from NMDAR blockade. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats

Four experiments examined the effects of excitotoxic, axon-sparing lesions of the medial prefrontal cortex or anterior cingulate cortex in rats on responding under different schedules of intravenous cocaine self-administration and on the locomotor stimulant effects of cocaine. Experiment 1 tested the acquisition and maintenance of cocaine self-administration under a fixed ratio schedule. Rats with medial prefrontal cortex lesions showed facilitated acquisition and enhanced responding for low doses of the drug when lesions were induced before self-administration behaviour was established. Lesions of the anterior cingulate cortex did not affect cocaine self-administration. In experiment 2, rats were trained to respond under a second-order schedule of cocaine reinforcement, where responding during the fixed interval was reinforced by presentation of a cocaine-associated visual stimulus under fixed-ratio contingencies. In control rats, these schedule conditions were found to maintain high rates of responding and a scalloped pattern of responding over time. Omission of conditioned stimulus presentation during the fixed interval significantly disrupted response patterns, confirming that the stimulus served to maintain responding during the fixed interval. By contrast, rats with medial prefrontal cortex lesions showed higher rates and disrupted patterns of responding that were unchanged by stimulus omission. Rats with lesions of the anterior cingulate cortex responded at high rates throughout the fixed interval under all test conditions, indicating that the cocaine-associated stimulus did not serve to maintain temporal patterns of responding in these rats. Experiment 3 demonstrated the lack of effect of either lesion on the acquisition of responding for a non-drug reinforcer, sucrose. In experiment 4, measures of spontaneous and cocaine-induced locomotor activity revealed that rats in both lesion groups were significantly more active than controls regardless of test conditions. These data indicate that facilitated acquisition of cocaine self-administration and disrupted response patterns under second-order schedule contingencies may result from deficits in behavioural inhibition induced by medial prefrontal cortical lesions that contrast with deficits following damage to other limbic cortical regions, such as the basolateral amygdala or anterior cingulate cortex.     

Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.

The present study examined the effects of lesions of the central nucleus of the amygdala (CeA) on the acquisition of a new response with conditioned reinforcement (CR) and its potentiation by intra-accumbens infusions of d-amphetamine (1, 3, 10, and 20 μg/μl). Rats were trained to associate a light-plus-noise compound stimulus with the availability of a sucrose solution before receiving both bilateral ibotenic acid lesions of the CeA and cannulas implanted above the nucleus accumbens. Lesions of the central nucleus did not impair the performance of positively reinforced discriminated approach, nor did they impair the acquisition of a new response with conditioned reinforcement. However, the potentiation of responding with CR following intra-accumbens amphetamine was blocked in lesioned animals. These results are discussed in terms of the possible interactions between associative mechanisms in the amygdala and the mesolimbic dopamine projection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the mediodorsal nucleus of the thalamus and classical eyeblink conditioning under less-than-optimal stimulus conditions: Role of partial reinforcement and interstimulus interval.

Rabbits received lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions and were subjected to classical eyeblink (EB) and heart rate (HR) conditioning. Separate groups of sham and lesioned animals received either 50% or 25% reinforcement with a periorbital shock unconditioned stimulus. Other groups received an interstimulus interval (ISI) of either 1.0 or 1.5 s. Animals with MD lesions acquired the EB conditioned response (CR) more slowly than sham-lesioned animals with either the 1.5-s ISI or with the 25% reinforcement schedule. The lesions had no significant effect on the HR CR, however. Results suggest that information processed by MD is relayed to the prefrontal cortex and is required for somatomotor response selection under nonoptimal learning conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disrupted temporal control in the R6/2 mouse model of Huntington’s disease.

Huntington’s disease is characterized by corticostriatal dysfunction and degeneration of the striatum with progressive loss of the medium spiny neurons. These circuits are important for instrumental responding, interval timing, and temporal control over motor output. We investigated the acquisition of timed operant responding in two R6/2 Huntington’s Disease models, differing in CAG repeat length and genetic background (115 and 250 CAG repeats, and a mixed CBAxC57 or pure C57 background) and their corresponding wild type controls using the peak procedure. Both mouse lines exhibited similar response control deficits. In unreinforced peak trials, mice either did not learn to terminate an ongoing response past reinforcement time or required more trials to acquisition compared to the wild type mice. While transgenic and wild type mice did not exhibit differences in temporal accuracy, response curves were flatter in transgenic mice, suggesting decreased temporal control over operant responding. The results are discussed in terms of the neurobiology of interval timing, instrumental responding, and the neuropathology of HD and R6/2 mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The pedunculopontine tegmental nucleus and responding for sucrose reward.

Pedunculopontine tegmental nucleus (PPTg) lesions in rodents lead to increased sucrose consumption, but the psychological deficit behind this remains uncertain. To understand better the relationship between consumption of, and motivation for, sucrose, the authors trained rats to traverse a runway for 20% or 4% sucrose solution; after 7 days, concentrations were reversed. Control rats consumed more 20% than 4% sucrose solution and promptly altered run times in response to concentration change. PPTg-lesioned rats consumed normal quantities of 4% but more 20% sucrose solution than controls and took longer to alter their runway time following the concentration change. These data suggest that lesions of the PPTg do not alter motivation per se and might be better understood as inducing a response selection deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical differential and operant conditioning in rabbits (Oryctolagus cuniculus) with septal lesions.

12 normal New Zealand white rabbits and 12 with septal lesions received classical differential conditioning of the nictitating membrane response (NMR), followed by auditory generalization tests run in extinction. Although rate of acquisition and asymptotic responding to positive conditioned stimuli did not differ, septals responded more than normals to nonreinforced stimuli. Resultant decrements in differential conditioning could not be attributed to changes in auditory or shock thresholds or to increased spontaneous NMRs. Septals also responded at higher rates in both operant conditioning (barpresses reinforced with food pellets on a variable interval schedule) and extinction sessions. No difference in suppression in a passive avoidance task was found. Results are discussed in relation to R. A. McCleary's (1966) response disinhibition analysis of septal function, and an habituation hypothesis is considered. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition, retention, and extinction of operant discriminations in rats with nucleus basalis magnocellularis lesions.

Effects of bilateral ibotenic acid lesions of nucleus basalis magnocellularis (NBM) and scopolamine treatment on different aspects of learning and memory in an operant discrimination task were assessed. In Experiment 1, NBM lesions impaired acquisition performance. In Experiment 2, scopolamine lowered response rates but did not affect discrimination accuracy in lesioned or control rats. In Experiment 3, although pretrained rats showed transient increases in commission errors, percentage correct responding remained above chance levels after lesion. During extinction in Experiment 4, operant responding diminished more quickly in pretrained NBM-lesioned rats than in controls, but subsequent reacquisition performance was equivalent in both groups. Results suggest the NBM is importantly involved in discrimination learning, but cholinergic activity may be less critical for memory retention than for acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine receptor blockade and extinction differentially affect behavioral variability.

Dopamine (DA) neurons respond to unexpected food delivery and are inhibited during the omission of expected reward. DA receptor blockade mimics some, but not all, aspects of nonreward (extinction) conditions. It was therefore of interest to ask whether DA receptor blockade produces extinction-like increases in behavioral variability in addition to its well-known operant response-suppressing effects. In the current experiment, rats were trained drug-free on an operant task in which they pressed on a keyboard. Two of the keys led to food on a continuous reinforcement schedule. Both response rates and behavioral variability were measured. Test day administration of D? and D? antagonists SCH23390 and raclopride, like extinction, suppressed responding but, unlike extinction, did not lead to an increase in variability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)