Effects of ethanol on Pavlovian autoshaping in rats

 Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession IP injections of ethanol doses (0.00, 0.25, 0.50, 0.70, or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1–5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11–15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol’s effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession IP injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered. Received: 15 December 1997 / Final version: 27 March 1998     

Acquisition and performance effects of scopolamine and of treatment withdrawal in avoidance situations

Two experiments were carried out in order to compare the effects of scopolamine on acquisition with those of changes of state in either direction (no drug to drug and vice versa). Two avoidance tasks the acquisition of which was known to be facilitated by small doses of tertiary antimuscarinics were used. The first study on continuous discriminated lever press avoidance, with either light onset or light offset as warning signal, showed a performance enhancement after the treatment of pretrained animals, and a performance decrement in animals trained in the drug state and then shifted to placebo. The data, however, also showed a partial carry-over of the scopolamine facilitation to the no drug condition, and a partial carry-over of the no drug retardation to the drug condition. The facilitation of acquisition (reduction of shock rate, enhancement of total response rate and of discriminated responses) and all other phenomena indicated above were more marked in the light off condition, which depressed acquisition and performance in untreated animals. The second experiment on discrete-trial two-way avoidance with light onset (non directional) as CS used a 2 × 2 × 2 × 2 design, combining the features of previous studies which had shown contrasting effects of changes of state, depending on various experimental conditions. A performance decrement after treatment withdrawal was again observed in all instances. However, this experiment confirmed that the performance effects of drug administration to pretrained animals depend both on the distribution of previous practice (single 250-trial session versus 5 sessions of 50 trials each) and on the interval between the end of training and the retest (1 day versus 14 days). These results and various literature data on antimuscarinics indicate that the contrasting effects of state changes cannot be explained by simple general models. In particular, these data exclude important state dependence phenomena in the case of these agents.     

The retention deficit induced by (RS)-α-methyl-4-carboxyphenylglycine in a lever-press learning task is blocked by selective agonists of either group I or group II metabotropic glutamate receptors

The effects of immediate post-training administration of drugs interacting with group I and/or group II glutamate metabotropic receptors (mGluRs) were determined on the retention performance of a partially acquired lever-press learning task in mice. The antagonist (RS)-α-methyl-4-carboxyphenylglycine (MCPG) dose-dependently (0.1–100 nmol/mouse, i.c.v.) impairs the retention performance evaluated 24 h post-training. The retention deficit induced by 100 nmol MCPG is related to the selective suppression of a time-dependent spontaneous improvement of performance between the two sessions. This phenomenon appears progressively within 24 h post-training in control mice and is thought to reflect post-training processing of memory traces. The coadministration of either (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), the group I mGluR agonist (R,S)3,5-dihydroxyphenylglycine (DHPG), or the group II mGluR agonist LY354740, completely blocked MCPG-induced deficits at a dose of 0.1 nmol for each agonist. These results suggest that selective activation of either group I or group II mGluRs is able to prevent the memory retention deficits induced by MCPG. Received: 27 January 1999 / Accepted: 27 May 1999     

Disturbance of rat lever-press learning by hippocampo-prefrontal disconnection

To determine whether the medial prefrontal cortex (PFC), ventral hippocampus and hippocampo-PFC pathway are involved in operant lever-press learning, we conducted lidocaine injections to these brain sites. Rats were injected immediately after lever-press acquisition in the first training, and the second 5-min test the next day. Results showed the response rate of either PFC- or ventral hippocampus-inactivated rats to be lower than that of control rats in the test the next day. Rats having lidocaine injected into the unilateral ventral hippocampus combined with contralateral medial PFC also showed lower response rate in their tests. These results suggest that hippocampo-PFC disconnection disturbs operant learning.     

Effects of d-amphetamine and cocaine on repeated acquisition with timeout from avoidance

The acute effects of d-amphetamine and cocaine on a repeated acquisition baseline with timeout from avoidance were investigated in two rats. Each session the animals acquired one of two different three-member response sequences. Each sequence member was associated with a different response lever. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout (30 sec) from avoidance. Incorrect responses did not postpone shock. The baseline performance was characterized by a decrease in errors within each session, similar to patterns of repeated acquisition maintained by food. In comparison to control sessions, both d-amphetamine and cocaine increased errors and altered the pattern of within-session acquisition. d-Amphetamine increased the rate of sequence completion and the rate of shock delivery in both animals. Cocaine increased the rate of sequence completion in one animal and increased the rate of shock delivery for the other.     

Avoidance perseveration during extinction training in Wistar-Kyoto rats: an interaction of innate vulnerability and stressor intensity

Given that avoidance is a core feature of anxiety disorders, Wistar-Kyoto (WKY) rats may be a good model of anxiety vulnerability for their hypersensitivity to stress and trait behavioral inhibition. Here, we examined the influence of strain and shock intensity on avoidance acquisition and extinction. Accordingly, we trained WKY and Sprague-Dawley (SD) rats in lever-press avoidance using either 1.0-mA or 2.0-mA foot-shock. After extinction, neuronal activation was visualized by c-Fos for overall activity and parvalbumin immunoreactivity for gamma-aminobutyric acid (GABA) neuron in brain areas linked to anxiety (medial prefrontal cortex and amygdala). Consistent with earlier work, WKY rats acquired lever-press avoidance faster and to a greater extent than SD rats. However, the intensity of foot shock did not differentially affect acquisition. Although there were no differences during extinction in SD rats, avoidance responses of WKY rats trained with the higher foot shock perseverated during extinction compared to those WKY rats trained with lower foot shock intensity or SD rats. WKY rats trained with 2.0-mA shock exhibited less GABAergic activation in the basolateral amygdala after extinction. These findings suggest that inhibitory modulation in amygdala is important to ensure successful extinction learning. Deficits in avoidance extinction secondary to lower GABAergic activation in baslolateral amygdala may contribute to anxiety vulnerability in this animal model of inhibited temperament.     

A behavioral analysis of force-controlled operant tasks in American lobster

Operant conditioning is a common tool for studying cognitive aspects of brain functions. As the first step toward understanding those functions in simple invertebrate microbrains, we tested whether operant conditioning could be applied to train American lobster Homarus americanus that has been extensively adopted as an animal model for neurophysiological analyses of nervous system functions and behavioral control. The animal was trained by food rewarding for gripping of a sensor bar as the operant behavior. Lobsters were first reinforced when they acted on the bar with a stronger grip than a pre-set value. After this reinforcement, the animal learnt to grip the bar for food pellets. The yoked control experiment in which the animal received action-independent reinforcement excluded the possibility of pseudoconditioning that the food simply drove the animal to frequent gripping of the sensor bar. The association of the bar-grip with food was extinguished by rewarding nothing to the operant behavior, and was restored by repeating the reinforcement process as before. In addition, lobsters successfully carried out differential reinforcement regarding the gripping force: their gripping force changed depending on the increased force threshold for food reward. These data demonstrate that lobsters can be trained by operant conditioning paradigms involving acquisition and extinction procedures with the precise claw gripping even under the force control.     

Ro 15-4513 selectively attenuates ethanol,but not sucrose,reinforced responding in a concurrent access procedure: comparison to other drugs

The experiments described in this report used a concurrent access procedure to study ethanol reinforcement. Rats were trained to lever press for a 10% sucrose solution and a 10% ethanol/10% sucrose mixture, and both reinforcers were available on variable-interval 5-s schedules. In baseline and vehicle injection sessions, the animals distributed their responding between both solutions. When injected with the partial inverse benzodiazepine agonist Ro 15-4513 (3, 9, and 18 mg/kg), responding for the ethanol solution decreased while responding for sucrose remained intact. Ethanol injections (0.5 and 1.0 g/kg) engendered a similar profile. Chlordiazepoxide led to an increase in ethanol mix responding at 2 mg/kg and a decrease in ethanol mix responding at higher doses; no dose affected sucrose responding. Morphine (0.5–16 mg/kg) decreased responding for both the ethanol mix and sucrose solutions, more or less simultaneously. Naloxone (0.125–20 mg/kg) selectively reduced ethanol mix responding at low doses, and decreased responding for both reinforcers at high doses. In another group of animals, isocaloric alternatives were concurrently available: 10% ethanol/0.25% saccharin versus 14% sucrose. Injections of Ro 15-4513 and chlordiazepoxide produced similar results as in the first group of rats: an increase in ethanol mix responding with low dose chlordiazepoxide, and a decrease in ethanol mix responding with Ro 15-4513. However, naloxone injections did not selectively affect responding for either of the reinforcers when they were isocaloric. These results are discussed in terms of ethanol's neuropharmacological actions.     

Enantioselective behavioral effects of threo-methylphenidate in rats.

The relative potency of d- and l-threo-methylpenidate (d-MPH and l-MPH) was evaluated using three behavioral paradigms for rats: Responding maintained by a fixed-interval schedule of reinforcement (FI), responding maintained by a concurrent variable-interval schedule of reinforcement (Conc VI VI), and consumption of sweetened condensed milk during a 15-min free-access period. In each case the potency of the d-MPH enantiomer greatly exceeded that of the l-MPH enantiomer. Temporal control of responding was reduced (FI), choice responding was equalized for most rats (Conc VI VI), and milk consumption was suppressed by d-MPH and dl-MPH.     

d-Amphetamine,operant history,and variable-interval performance

The effects of d-amphetamine on the bar-pressing of rats maintained under a variable-interval schedule of water reinforcement were examined as a function of the operant history of the subjects. One group of rats initially received 51 sessions of exposure to a fixed-ratio 20 schedule, while a second group received equivalent exposure to an interresponse-time-greater-than-12-sec schedule. Mean group response rate when stable was over ten times as high under the fixed-ratio schedule as under the interresponse-time-greater-than-12-sec schedule. Response rates of the two groups largely converged across 47 sessions of exposure to a variable-interval 60-second schedule, at which time response rates for both groups appeared stable. Acute administrations of d-amphetamine sulfate similarly affected mean response rates of both groups: A 0.25 mg/kg dose did not obviously affect rate, while doses of 0.5, 1.0, and 2.0 mg/kg produced dose-dependent rate decreases. These results indicate that the efficacy of operant history as a determinant of drug effects may be limited to circumstances where current contingencies do not exercise powerful and direct control over behavior.