Nicotine's enhancing effects on responding maintained by conditioned reinforcers are reduced by pretreatment with mecamylamine, but not hexamethonium, in rats.

Several studies have indicated that nicotine increases responding maintained by conditioned reinforcers. We assessed the effects of subcutaneous injections of 0.3 mg/kg nicotine and two nicotinic antagonists on responding maintained by conditioned and primary reinforcers and responding during extinction in 8 Long Evans rats. Mecamylamine, a central and peripheral nicotinic antagonist, and hexamethonium, a peripheral nicotinic antagonist, were administered prior to a subset of the experimental sessions. Nicotine selectively increased responding maintained by conditioned reinforcers and mecamylamine, but not hexamethonium, attenuated this effect. These results suggest that nicotine's enhancing effect on responding maintained by conditioned reinforcers is mediated in the central nervous system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of nicotine-induced seizures in rats by combining vaccination against nicotine with chronic nicotine infusion.

The ability of a nicotine vaccine to protect against nicotine-induced seizures was studied in rats. Groups of 10 rats were vaccinated with 3 doses of either a nicotine conjugate vaccine over 6 weeks to elicit high titters of nicotine-specific antibodies or with a control vaccine. Rats were then pretreated with a 1-weekk subcutaneous infusion of either nicotine 1 mg/kg/day or saline and then received a single 2 mg/kg ip dose of nicotine to provoke seizures. Vaccination reduced the incidence of seizures. The combination of vaccination and pretreatment with nicotine infusion was more effective than either treatment alone. These data suggest that vaccination is protective against this toxic effect of nicotine and that combining vaccination and chronic nicotine administration may provide a novel strategy for blocking some effects of nicotine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of D-cycloserine on extinction of conditioned freezing.

The present study tested the prediction that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, would facilitate extinction of conditioned freezing in male Sprague-Dawley rats. Rats received 5 light-shock pairings (conditioning). The following day, rats received 6 light-alone presentations (extinction training). Twenty-four hours later, rats received 1 light-alone presentation (test). Subcutaneous DCS injection before or after extinction training significantly enhanced extinction, and the dose-response curve for this effect was linear. Increasing the delay of DCS administration after extinction training led to a linear decrease in the facilitatory effect. The effect of systemic administration was replicated by intra-basolateral amygdala infusion. These results suggest that DCS facilitates extinction of conditioned freezing by acting on consolidation processes partly mediated by the basolateral amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of eyeblink conditioned response timing in rats.

Eyeblink conditioned response (CR) timing was assessed in adult and infant rats. In Experiment 1, adult rats were trained with a 150-ms tone conditioned stimulus (CS) paired with a periorbital shock unconditioned stimulus (US; presented at 200- or 500-ms interstimulus intervals [ISIs]). The rats acquired CRs with 2 distinct peaks that occurred just before the US onset times. Experiments 2 and 3 examined developmental changes in CR timing in pups trained on Postnatal Days 24-26 or 32-34. Experiment 3 used a delay conditioning procedure in which the tone CS continued throughout the ISIs. Pups of both ages exhibited robust conditioning. However, there were age-related increases in the percentage of double-peaked CRs and in CR timing precision. Ontogenetic changes in eyeblink CR timing may be related to developmental changes in cerebellar cortical or hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motivated attention and prepulse inhibition of startle in rats: Using conditioned reinforcers as prepulses.

In humans, prepulse inhibition (PPI) of startle is greater during attended prestimuli than it is during ignored prestimuli, whereas in rats, most work has focused on passive PPI, which does not require attention. In the work described in this article, researchers developed a paradigm to assess attentional modification of PPI in rats using motivationally salient prepulses. Water-deprived rats were either conditioned to attend to a conditioned stimulus (CS; 1-s, 7-dB increase in white noise) paired with water (CS+ group), or they received uncorrelated presentations of white noise and water (CSo group). After 10 conditioning sessions, startle probes (50 ms, 115 dB) were introduced, with the CS serving as a continuous prepulse. Three experiments examined PPI across a range of prepulse intensities (4-10 dB) and stimulus onset asynchronies (SOAs; 30-960 ms). PPI was consistently reduced in the CS+ group, particularly with a 10-dB prepulse and a 60-ms SOA. Thus, PPI in rats differed between attended and ignored prestimuli, but the effect was reversed in the results of research with humans. A fourth study eliminated the group difference by reversing the CS-water contingency. Methodological and motivational hypotheses regarding the current findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2×2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability.

Conditioned stimuli (CSs) can control behavior either by activating responses when presented noncontingently or through their ability to maintain responding when presented contingently, that is, as conditioned reinforcers. In the present study, the extent to which drug-seeking behavior could be subject to these different types of stimulus control was studied by presenting to rats CSs that were either paired with each drug infusion or presented as discriminative stimuli (DSs) signaling the availability of drug. It was found that stimuli paired with either cocaine or heroin infusions increased drug seeking when presented contingent on responding, but not when presented noncontingently. By contrast, DSs that signaled cocaine availability increased drug seeking when presented either noncontingently or contingently. These results suggest that drug-seeking behavior can be influenced differentially by CSs and that conditioned reinforcers are especially important for maintaining prolonged sequences of drug-seeking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of adolescent nicotine exposure on opioid consumption and neuroendocrine response in adult male and female rats.

Effects of adolescent nicotine exposure on illicit drug consumption and neuroendocrine functioning were examined in adult rats. Nicotine (NIC; 2 doses) or saline (SAL) was administered via osmotic minipumps to 30 male and 30 female adolescent Wistar rats for 19 days. After NIC/SAL cessation, oral opioid consumption was assessed in the home cage for 4 weeks. Plasma corticosterone and ACTH were measured at the end of the experiment. Low-NIC male rats consumed more fentanyl than did high-NIC male rats; opioid consumption among adult female rats was not altered by NIC exposure. Females consumed more fentanyl than did males, regardless of NIC history. NIC exposure increased adult corticosterone and ACTH levels in a dose-dependent manner. Results suggest important effects of adolescent NIC exposure, including altered neuroendocrine status and opioid consumption. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial dorsal thalamic lesions impair blocking and latent inhibition of the conditioned eyeblink response in rats.

The effects of lesions of the medial dorsal thalamic nucleus (MD) on blocking and latent inhibition (LI) of the rat eyeblink response were examined in the present study. Previous work has demonstrated that the cingulate cortex and related thalamic areas are involved in processing conditioning stimuli throughout training. The experiments in the present study tested the hypothesis that disruption of cingulothalamic stimulus processing produced by lesions of the MD would impair 2 types of associative learning that involve decremental changes in attention. In Experiment 1, MD lesions severely impaired blocking. In Experiment 2, NM lesions severely impaired LT. The results indicate that lesions of the NM impair incremental, decremental, or both types of changes in stimulus processing during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of posttraining damage to the pedunculopontine tegmental nucleus on conditioned stimulus transfer in two-way active avoidance in rats.

The effects of posttraining excitotoxic lesions of the pedunculopontine tegmental nucleus (PPTg) on two-way active avoidance after changing the conditioned stimulus (CS) used during prelesion training were examined. Prelesion training was carried out with either a tone or a light as the CS, and this CS was changed during postlesion training. Replacing the tone with a light reduced the performance of control and lesioned rats, but the degree of reduction was higher in the latter. Replacing the light with a tone had slight detrimental effects in lesioned rats but not in controls. Thus, posttraining PPTg lesions slowed down the reacquisition of shuttle-box avoidance under conditions of CS transfer, an effect that may be attributable to disruption of attention and/or gating of sensory stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of nicotine deprivation on craving response covariation in smokers.

Most models of craving propose that when cravings are strong, diverse responses--thought to index an underlying craving state--covary. Previous studies provided weak support for this hypothesis. The authors tested whether nicotine deprivation affects degree of covariation across multiple measures related to craving. Heavy and light smokers (N=127) were exposed to smoking cues while either nicotine deprived or nondeprived. Measures included urge ratings, affective valence, a behavioral choice task assessing perceived reinforcement value of smoking, and smoking-related judgment tasks. Results indicated higher correlations in the nicotine-deprived than in nondeprived group. The measures principally responsible for this effect loaded onto a single common Craving factor for nicotine-deprived but not nondeprived smokers. These findings suggest that, under certain conditions, measures of craving-related processes covary. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of acute and prolonged opiate abstinence on extinction behaviour in rats.

We examined the role of withdrawal in relapse to drug-seeking and drug-taking by testing the effects of opiate abstinence on extinction behaviour in rats trained to self-administer heroin. Male Long-Evans rats responded for IV heroin under a heterogeneous chain (VI 120 s; FR 1) schedule in which "seeking" responses preceded a "taking" response which produced a drug infusion. Responding was then measured in extinction during acute (6, 12, and 24 hr) and prolonged (3, 6, 12, and 25 day) abstinence. Sucrose consumption and somatic withdrawal were assessed at each testing period. During acute abstinence, responses on the "drug-seeking" manipulandum increased at 24 hr, whereas responses on the "drug-taking" manipulandum increased at 6 hr. Both responses were elevated during the 12-day abstinence test. Sucrose consumption was reduced and somatic withdrawal scores were increased in opiate-experienced rats at each test period. Results suggest that heroin abstinence has different effects on drug-seeking and drug-taking and that these effects do not temporally coincide with somatic measures of opioid withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporally specific extinction of conditioned responses in the rabbit (Oryctolagus cuniculus) nictitating membrane preparation.

Extinguishing a conditioned response (CR) has entailed separating the conditioned stimulus (CS) from the unconditioned stimulus (US). This research reveals that elimination of the rabbit (Oryctolagus cuniculus) nictitating membrane response occurred during continuous CS-US pairings. Initial training contained a mixture of 2 CS-US interstimulus intervals (ISIs): 200 ms and 1,200 ms. The CRs showed double peaks, one for each ISI. When 1 ISI was removed, its CR peak showed the hallmarks of extinction: a decline across sessions, spontaneous recovery between sessions, and rapid reacquisition when the absent ISI was reintroduced. These results support real-time models of conditioning that segment the CS into microstimuli while challenging theories that rely on contextual control, US representations, CS processing, and response inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: Role of D2 and D3 receptor subtypes.

Neonatal quinpirole treatment in rats produces increased sensitivity of dopamine D2-like receptors throughout the animal’s lifetime, referred to as D2 priming. There is little information on the effects of nicotine in adolescent rats, especially in a model that has clinical relevance to psychosis where increased D2 receptor sensitivity is common. Male and female rats were treated with quinpirole (1 mg/kg) or saline from postnatal (P) day 1–P21, given nicotine (0.5 mg/kg) or saline from P33 through P49, and placed into a locomotor arena for behavioral testing. Nicotine or saline treatment was preceded by the D2-like receptor antagonist eticlopride, D3 antagonist nafadotride, or saline. Conditioned hyperactivity was analyzed on P50 in the same context in a drug-free test. In females, D2 priming increased the locomotor response to acute nicotine, but did not affect subsequent nicotine sensitization, and only non–D2-primed females demonstrated conditioned hyperactivity. Eticlopride and nafadotride blocked behavioral sensitization, although nafadotride was more effective at blocking nicotine-conditioned hyperactivity in females. In males, D? priming enhanced sensitization to nicotine and produced conditioned hyperactivity, which were blocked by eticlopride and nafadotride. These results have implications for psychosis and comorbidity of nicotine abuse in adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motivational control of heroin seeking by conditioned stimuli associated with withdrawal and heroin taking by rats.

The authors investigated the impact of conditioned withdrawal on drug seeking by training rats to work for a heroin infusion on a seeking-taking schedule, which required responding on a seeking lever in order to gain the opportunity to self-administer the drug by a single response on a taking lever. Following the establishment of opiate dependence, a conditioned stimulus (CS) that had been previously paired with naloxone-precipitated withdrawal suppressed heroin seeking in extinction. However, when the rats had prior experience of heroin taking in the presence of the withdrawal CS, drug seeking was elevated in the presence of this stimulus. The authors conclude that the conditioned motivation of drug seeking in withdrawal depends on previous association of the CS with drug taking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Familiarity-based stimulus generalization of conditioned suppression in rats is dependent on the perirhinal cortex.

We report that bilateral, excitoxic lesions of the perirhinal cortex attenuate rats' familiarity-based stimulus generalization. After surgery, rats were preexposed either to 2 auditory stimuli (A and B) or to only 1 auditory stimulus (B). Following preexposure, all rats received pairings of A and a footshock before assessment of generalized responding (conditioned suppression) to B. Sham rats' generalization was greater when preexposure was to both A and B than when preexposure was to B only. That pattern was abolished in lesioned rats, though no general deficiency was found in other measures of auditory processing. Our findings suggest that the perirhinal cortex is required for rats to encode familiarity as part of stimulus representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic morphine treatment on responding for intracranial stimulation in female versus male rats.

Morphine was administered to Sprague-Dawley rats twice daily at 0, 3, 10, and 20 mg/kg injection during Weeks 1, 2, 3, and 4, respectively; responding for medial forebrain bundle stimulation was assessed 1, 2, and 3 hr after morning injections in female versus male rats. There were no sex differences in responding under control conditions (Week 1). Morphine's effect on response rate depended on dose, time post-injection, stimulation frequency, and day of treatment. Significant sex differences in morphine's effects occurred at 10 mg/kg, which decreased responding more in males at 1 hr and increased responding more in females at 2 hr, at some frequencies and on some test days. Similar trends were observed at other frequencies, test days, and doses. Morphine's differential effect in males versus females in this procedure suggests that sex comparisons of opioid effects in many animal models may be influenced by sex difference in opioid effects on behavior output. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of nicotine on attention and inhibitory control in healthy nonsmokers.

Nicotine improves cognitive functioning in smokers and psychiatric populations, but its cognitive-enhancing effects in healthy nonsmokers are less well understood. Nicotine appears to enhance certain forms of cognition in nonsmokers, but its specificity to subtypes of cognition is not known. This study sought to replicate and extend previous findings on the effects of nicotine on cognitive performance in healthy nonsmokers. Healthy young adults (N = 40, 50% women) participated in a placebo-controlled, double-blind, repeated measures experiment examining the effects of 7 mg transdermal nicotine or placebo. Participants completed tests of attention (Attention Network Test), behavioral inhibition (stop signal task, Stroop test), reward responsiveness (signal detection task), and risk-taking behavior (Balloon Analogue Risk Task). Physiological (heart rate, blood pressure) and subjective (Profile of Mood States, Drug Effects Questionnaire) measures were also obtained. Nicotine significantly improved performance only on the Stroop test, but it impaired performance on one aspect of the Attention Network Test, the orienting effect. Nicotine produced its expected effects on physiologic and subjective measures within the intended time course. The findings of this study contribute to a growing literature indicating that nicotine differentially affects specific subtypes of cognitive performance in healthy nonsmokers. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of a Corneal Anesthetic on Extinction of the Classically Conditioned Nictitating Membrane Response in the Rabbit (Oryctolagus cuniculus).

Rabbits (Oryctolagus cuniculus) were presented with 7 daily sessions of tone-alone training after conditioning. Before the beginning of each of the first 4 extinction sessions, an artificial tear solution or tetracaine hydrochloride was administered to the cornea of rabbits in the control group (n=6) and experimental group (n=1), respectively. There were no between-group differences in the percentage of conditioned responses between both groups. However, the amplitude of the conditioned response was notably reduced in the tetracaine group (M=0.40, SEM±0.216) relative to the control group (M=1.32, SEM ±0.639) early in extinction. Results seem to suggest that although motor output has been found to play an important role in extinction, corneal sensory feedback is not necessary. (PsycINFO Database Record (c) 2010 APA, all rights reserved)