Testosterone potentiates scopolamine-induced disruptions of nonspatial learning in gonadectomized male rats.

Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperstriatal lesions and classical conditioning in the pigeon.

In two experiments, pigeons with bilateral lesions of the hyperstriatum were compared with unoperated control birds and operated control subjects having bilateral lesions of the neostriatum on tasks designed to test two hypotheses of hyperstriatal function. In Experiment 1, hyperstriatal lesions impaired both the acquisition and maintenance of autoshaped responding as well as maintenance responding in response-omission training. In Experiment 2, hyperstriatal birds displayed depressed levels of responding relative to control birds on a classical go-no-go alternation schedule. These results support the view that hyperstriatal lesions selectively disrupt classical conditioning and go against the view that hyperstriatal lesions exaggerate perseverative responding. A surprising aspect of the results was the performance of the operated control subjects that showed better performance in the acquisition of autoshaping and superior differentiation on the go-no-go schedule compared with the unoperated control birds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estrogen improves response accuracy and attenuates the disruptive effects of Δ?-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance.

Despite evidence of an interaction between cannabinoids and estrogen in the brain, little information is available regarding the consequences of this interaction on behavior. A within-subjects design was used to examine the effects of estrogen and Δ?-tetrahydrocannabinol (Δ?-THC) on learning and memory in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Treatment with low physiological levels of estrogen, delivered in Silastic capsules, improved response accuracy without affecting response rate during acquisition. Estrogen also attenuated the ability of Δ?-THC (0.56-3.2 mg/kg) to decrease response accuracy and rate during acquisition and response accuracy during performance. Results indicate that estrogen can improve accuracy during acquisition of a nonspatial operant task and can attenuate Δ?-THC-induced behavioral deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of pedunculopontine tegmental nucleus lesions on responding for intravenous heroin under different schedules of reinforcement

The pedunculopontine tegmental nucleus (PPTg) is believed to play important roles in reward and learning. We examined the effect of PPTg lesions (0.5 microl of 0.1 M NMDA injected bilaterally over 10 min) on the learning of an operant response for opiate reward. In 14 adult male Long-Evans rats, bilateral lesions of the PPTg disrupted the acquisition of responding for intravenous heroin (0.1 mg/kg infused at a rate of 0.25 ml/28 sec) on a fixed ratio-1 (FR-1) schedule of reinforcement. The 12 remaining lesioned animals increased their heroin intake over the acquisition sessions but did not reach the response levels of sham-lesioned animals on the 15th and final session. The sham- and PPTg-lesioned animals that learned the FR-1 task exhibited similar patterns of responding during extinction and reacquisition sessions. When tested on a progressive ratio (PR) schedule of reinforcement, however, PPTg-lesioned animals had lower break points than sham-lesioned animals. Asymmetric lesions, which destroyed the majority of the nucleus in one hemisphere only, did not produce any behavioral deficits. Rats that were lesioned after training also did not show deficits in responding under either FR or PR schedules. These findings suggest that PPTg lesions reduce the rewarding effect of opiates but do not disrupt the ability either to learn an operant response or the response requirements of a PR schedule.     

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.     

Reduced age differences in omission errors after prolonged exposure to response pacing contingencies.

Operant methods were used to study 4 older (62–74 yrs) and 4 younger (18–22 yrs) males under schedules in which monetary reinforcement depended on emission of complex response sequences; in 1 component of the schedule a new sequence was required for each session, but in the other component the sequence never changed. In line with previous research, placing time limits on responding initially disrupted the behavior of the older Ss but not that of the younger ones. Disruption was greater in acquisition of novel sequences than in performance of the established one and was evidenced more in failures to respond (omission errors) than in commission of errors. However, after extended exposure to each of several time limits, age differences were substantially reduced. Procedures that did not allow response correction after an error led to greater learning and smaller age differences than procedures that did allow error correction. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of 3,3'-iminodipropionitrile on acquisition and performance of spatial tasks in rats

3,3'-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 mg/kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit.     

Effects of phencyclidine, pentobarbital, and d-amphetamine on the acquisition and performance of conditional discriminations in monkeys

In each of two components of a multiple schedule, monkeys were required to respond on a right or left lever depending upon the stimulus combination (a color and a geometric form) presented. Reinforcement of a response in the presence of one stimulus (the form) was therefore conditioned upon the other stimulus (the color). The completion of a two-member chain of discriminations produced a food pellet. Errors produced a brief timeout. One composition of the multiple schedule was a repeated-acquisition task where the discriminative stimuli for left- or right-lever responses changed each session (learning). In the other component, the discriminative stimuli for left- or right-lever responses were the same each session (performance). Phencyclidine, pentobarbital, and d-amphetamine each produced dose-related decreases in the overall rate of responding in both components of the multiple schedule. At high doses each drug increased the percent errors in each component. At lower doses, however, the three drugs produced selective effects on accuracy. Errors were increased in the learning component at lower doses than those required to disrupt the discrimination in the performance component. A signal detection analysis of the data revealed that none of the drugs tested increased errors by selectively affecting either discriminability or bias.     

Estradiol replacement in gonadectomized male rats alters scopolamine-induced disruptions of nonspatial learning.

Recent evidence indicates that testosterone can modulate learning in males through an interaction with the cholinergic system. However, the mechanism for this interaction between testosterone and the cholinergic system on learning remains uncharacterized and may involve several of testosterone's active metabolites. In the present study, two of the active metabolites of testosterone, 5α-dihydrotestosterone and estradiol, were administered in combination with the muscarinic receptor antagonist scopolamine (0.1-1 mg/kg, i.p.) to adult gonadectomized male rats that were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences. In the acquisition component, subjects acquired a different three-response sequence each session, whereas in the performance component they responded on the same three-response sequence each session. When scopolamine was administered, it produced greater rate-decreasing and error-increasing effects in gonadally intact subjects than in gonadectomized subjects, even though gonadectomy had little or no effect on these measures under control conditions. In gonadectomized rats receiving 5α-dihydrotestosterone replacement, the disruptions produced by scopolamine were also smaller than those produced in gonadally intact subjects. In contrast, gonadectomized rats receiving estradiol replacement were as sensitive, or more sensitive, to scopolamine-induced disruptions of response rate and accuracy than those under the gonadally intact condition. These results suggest that testosterone's interactive effects with the cholinergic system on learning in gonadectomized male rats may not be mediated directly via androgen receptors, but rather by estrogen receptors following the aromatization of testosterone to estradiol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactive effects of training condition and septal lesions on perseverative responding in the rat.

In a study with 30 male Wistar rats, Ss that had received septal lesions either prior to acquisition of a position habit (Group SAR) or immediately after position habit acquisition (Group SR) were tested on 2 reversals of the task. Compared with control-operated Ss, both groups of Ss with septal lesions exhibited position-habit reversal deficits. The 2 groups with septal lesions could not be distinguished in terms of the total number of errors made during reversal learning, but could be distinguished on the basis of the type of error committed. Compared with Group SR, Group SAR made significantly more perseverative errors on the 1st reversal and significantly fewer perseverative errors on the 2nd reversal. Group SR made significantly more nonperseverative errors than Group SAR on both reversals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of spatial impairments and perseveration following selective prefrontal lesions in rats.

Reports results of 2 experiments with 27 male Wistar and 27 male hooded Long-Evans rats. Lesions to the medial frontal cortex produced severe deficits on spatial reversal learning and on delayed response, while lesions of the orbital frontal cortex produced perseverative response tendencies on a differential reinforcement of low rates 20-sec schedule and on barpressing extinction. Results are strikingly similar to those resulting from dorsolateral frontal and orbital frontal lesions, respectively, in rhesus monkeys. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuation of reversal deficits of mice with septal lesions by shifts in the motivational context.

Response perseveration following septal lesions (SLs), demonstrated on tasks that require change of a learned pattern of responding, depends in part on a relatively constant motivational context. The present experiment examined the effects of concurrent changes in the temperature of the water in a water-escape maze and the reversal of a spatial discrimination in 83 male Binghamton heterogeneous mice that had received either SLs or control surgery. Control and experimental Ss were trained on a spatial discrimination in either 17 or 34°C water. Following acquisition, reversal training was conducted in the maze filled with the same temperature water used during acquisition, or both water temperature and spatial reinforcement contingencies were reversed. When the water temperature remained constant across acquisition and reversal, Ss with SLs showed persistence during reversal training. Changing the water temperature concurrently with the institution of reversal training attenuated the perseverative deficits of Ss with SLs, in contrast to the relative lack of effect in controls. The role of the septal region in attention is discussed. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cytoskeleton of the vertebrate smooth muscle cell

Four experiments were conducted to determine the effects of dopamine (DA) antagonists and DA depletions on progressive-ratio responding for food reinforcement. On this schedule, ratio requirement increased by one response after each reinforcer was obtained, and rats were tested in 30-min sessions. Response rates and highest ratio completed were reduced in a dose-related manner by systemic injections of the D1 antagonist SCH 23390, and also by the D2 antagonists haloperidol and raclopride. Drug-treated rats also showed reductions in time to complete the last ratio, demonstrating that they had stopped responding before the end of the session. DA depletions produced by injections of 6-OHDA directly into the nucleus accumbens substantially decreased both the number of responses and the highest ratio completed. The deficits in response number and highest ratio completed induced by DA depletions persisted through the first 3 weeks of postsurgical testing, with some recovery by the fourth week. However, the deficits resulting from dopamine depletions were largely a manifestation of a decrease in response rate; although time to complete the last ratio was significantly reduced by dopamine depletions in the first few days of testing, rats recovered on this measure by the fifth day after surgery. Although previous work has shown that performance on several schedules (e.g., continuous, low value ratios, variable interval) is relatively unaffected by accumbens DA depletions, the present data demonstrate that such depletions do produce a substantial and persistent impairment of progressive ratio response output. Rats with accumbens DA depletions appear to have deficits in maintaining the high work output necessary for responding at large ratio values. The relative sparing of responding on some simple schedules, together with the present progressive ratio results, suggest that rats with accumbens DA depletions remain directed toward the acquisition and consumption of food, but they show deficits in work output for food.     

Stressor-provoked behavioral changes in six strains of mice.

Behavioral changes induced by inescapable shock were examined in 6 strains of mice. Exposure to shock provoked time-dependent disturbances of shuttle escape performance. In some strains the shock treatment did not affect escape performance, whereas in others profound performance deficits were evident. The inescapable shock treatment induced strain-dependent alterations of performance in a forced-swim task. In most instances the shock treatment initially provoked invigorated responding, but in other strains the shock had no effect or depressed active responding. Y-maze spontaneous alteration performance was not affected by the shock treatment, although a strain-dependent increase of perseverative responses was evident. The occurrence of a stressor-induced deficit in 1 task in a particular strain was not predictive of behavioral alterations in a 2nd task. Data are discussed with respect to animal models of depression and genetic differences associated with response to stressors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Punished behavior: increases in responding after d-amphetamine

Responding maintained in squirrel monkeys under a 10-min fixed-interval schedule of food presentation was suppressed by presenting a shock after every 30th response (punishment). During alternate 10-min periods of the same experimental session, but in the presence of a different discriminative stimulus, responding either had no effect (extinction) or postponed delivery of an electric shock (avoidance). During sessions when the avoidance schedule was not in effect, d-amphetamine sulfate decreased punished responding. When the avoidance schedule was present during alternate 10-min periods, however, d-amphetamine (0.01 minus 0.56 mg/kg, i.m.) markedly increased responding during punishment components. Increases in responding during avoidance components were also evident. The effects of d-amphetamine on punished responding depend on the context in which that responding occurs.     

Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability.

The authors examined set-shifting abilities in rats injected with antagonists of N-methyl-D-aspartate (NMDA) receptors (MK801) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (LY293558) into the medial prefrontal cortex (mPFC). Set-shifting was assessed with a maze-based task requiring a switch between brightness and texture discrimination strategies. Intra-mPFC injection of MK801 prior to training on the 2nd discrimination impaired discrimination strategy acquisition. The MK801-induced deficit was due to increased perseverative responding. AMPA receptor blockade also impaired acquisition of the 2nd discrimination, these impairments were due to more general cognitive deficits. Results suggest that, within the mPFC, both AMPA and NMDA receptors are necessary for set-shifting, and that NNMA receptor hypofunction impairs the capacity to modify existing knowledge or to inhibit responses that are no longer appropriate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulation and antagonism of opioid !d-receptors produce opposite effects on active avoidance conditioning in mice.

The effects of opioid δ-receptor activation on conditioning in a one-way active avoidance paradigm were investigated in mice. Peripheral administration of 30 and 100 μg/kg of [Leu–5] enkephalin (LE) and 11.6 μg/kg of [D-Pen–2,D-Pen–5]enkephalin ({dpdpe}), a synthetic enkephalin analog with high δ-selectivity, impaired acquisition of avoidance responding. The dose response functions for both peptides were U-shaped. Deficits in responding were also present 24 hours after training, which suggests that the impaired performance observed during training was not an impairment in the ability of the mice to perform. Also, neither LE nor {dpdpe} decreased footshock sensitivity or open-field activity, which rules out analgesia and decreased activity levels as likely explanations for the deficits in conditioning. Finally, antagonizing endogenous ligands with the δ-selective antagonist ICI 154,129 enhanced acquisition, an effect opposite that produced by LE and {dpdpe}. The results suggest that activation of δ-receptors is normally involved in the modulation of active avoidance learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of intracisternal 6-hydroxydopamine treatment on acquisition and performance of rats in a double T-maze.

136 male Sprague-Dawley rats in 4 experiments were subjected to various treatments with 6-hydroxydopamine (6-OHDA) to produce decrements in brain catecholamine content either before or after learning to respond in an appetitively motivated double –T maze task. Intracisternal injections of 6-OHDA not only impaired acquisition of the required behavioral response but also decreased performance of Ss which had previously acquired the task. Although reduced food consumption found in 6-OHDA-treated Ss may contribute to the observed deficits in –T maze responding, the behavioral deficit produced by 6-OHDA injection did not seem to be due only to a simple decrease in food intake. The decrements in acquisition and performance were clearly related to amount of central catecholamine depletion produced by 6-OHDA treatment. Further analysis suggested that the behavioral deficits were more related to the reductions in dopamine than they were to the depletion of brain norepinephrine. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Possible amotivational effects following marijuana smoking under laboratory conditions.

Human participants earned money by responding on a progressive-ratio (PR) schedule (initial value $50) or received money without responding on a fixed-time (FT) schedule. During the session, participants could terminate the PR schedule and initiate an FT 200-s schedule. In Experiment 1, increases in monetary value produced increased number of responses, time spent, and money earned in the PR component. In Experiment 2, marijuana smoking produced potency-related reductions in the number of responses, time spent, and money earned in the PR component, effects that can be interpreted as amotivational. Increasing the monetary value of the reinforcer diminished the acute marijuana effects on PR responding, suggesting that marijuana exerted an effect primarily on reinforcers of a smaller magnitude. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal lesions and associated learning in the pigeon.

The performance of pigeons with hippocampal lesions was compared with that of unoperated and neostriatal-lesioned control Ss in 3 experiments. In Experiment 1, hippocampal-lesioned birds were retarded in the acquisition and the maintenance levels of autoshaped responding. However, the deficit was attenuated following the addition of a response contingency to the autoshaping schedule. In Experiment 2, the hippocampal-lesioned birds showed impaired performance on a differential reinforcement of low rates of responding schedule. From the high levels of responding in Experiment 2, underresponding was observed in hippocampal-lesioned birds relative to control Ss on return to the autoshaping schedule in Experiment 3. Results are interpreted in terms of impaired classical conditioning in hippocampal-lesioned birds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)