Are cocaine-seeking “habits” necessary for the development of addiction-like behavior in rats?

Drug self-administration models of addiction typically require animals to make the same response (e.g., a lever-press or nose-poke) over and over to procure and take drugs. By their design, such procedures often produce behavior controlled by stimulus-response (S-R) habits. This has supported the notion of addiction as a “drug habit”, and has led to considerable advances in our understanding of the neurobiological basis of such behavior. However, for addicts to procure drugs, like cocaine, often requires considerable ingenuity and flexibility in seeking behavior, which, by definition, precludes the development of habits. To better model drug-seeking behavior in addicts we first developed a novel cocaine self-administration procedure (the Puzzle Self-Administration Procedure; PSAP) that required rats to solve a new puzzle every day to gain access to cocaine, which they then self-administered on an Intermittent Access (IntA) schedule. Such daily problem-solving precluded the development of S-R seeking habits. We then asked whether prolonged PSAP/IntA experience would nevertheless produce ‘symptoms of addiction’. It did, including escalation of intake, sensitized motivation for drug, continued drug use in the face of adverse consequences and very robust cue-induced reinstatement of drug-seeking, especially in a subset of ‘addiction-prone’ rats. Furthermore, drug-seeking behavior continued to require dopamine neurotransmission in the core of the nucleus accumbens (but not the dorsolateral striatum). We conclude that the development of S-R seeking habits is not necessary for the development of cocaine addiction-like behavior in rats

Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75023/1/j.1460-9568.1999.00576.x.pd

Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine

Repeated intermittent exposure to cocaine results in the neurochemical sensitization of dopamine (DA) transmission within the nucleus accumbens (NAc). Indeed, the excitability of DA neurons in the ventral tegmental area (VTA) is enhanced within hours of initial psychostimulant exposure. However, it is not known if this is accompanied by a comparably rapid change in the ability of cocaine to increase extracellular DA concentrations in the ventral striatum. To address this question we used fast-scan cyclic voltammetry (FSCV) in awake-behaving rats to measure DA responses in the NAc shell following an initial intravenous cocaine injection, and then again 2-hours later. Both injections quickly elevated DA levels in the NAc shell, but the second cocaine infusion produced a greater effect than the first, indicating sensitization. This suggests that a single injection of cocaine induces sensitization-related plasticity very rapidly within the mesolimbic DA system

Morphine alters the structure of neurons in the nucleus accumbens and neocortex of rats

Rats were given repeated injections of 10 mg/kg of morphine and were then left undisturbed for 24–25 days before their brains were processed for Golgi-Cox staining. Prior exposure to morphine decreased the complexity of dendritic branching and the number of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens and on pyramidal cells in the prefrontal and parietal cortex. It is suggested that some of the long-term behavioral consequences of repeated exposure to morphine may be due to its ability to reorganize patterns of synaptic connectivity in the forebrain. Synapse 33:160–162, 1999. © 1999 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34985/1/6_ftp.pd

The sensory features of a food cue influence its ability to act as an incentive stimulus and evoke dopamine release in the nucleus accumbens core

The sensory properties of a reward-paired cue (a Conditioned Stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track;” ST), approach to the location of reward delivery (rats that “goal-track;” GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs continued to approach the lever location, but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates.” Furthermore, the ability of both the lever-CS and reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever – dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility

Sex-typed attitudes, sex-typed contingency behaviors, and personality characteristics of male caregivers

The present study was designed to investigate the sex-typed attitudes, sex-typed contingency behaviors, and personality characteristics of male caregivers. The data for sex-typed attitudes were collected from The Sex-Typed Attitude Checklist, drawn from a study by Williams and Bennett (1975). The Adjective Check List (Gough & Heilbrun, 1965) assessed the personality characteristics of the respondents, and The Fagot-Patterson Checklist (1969) was employed to determine the sex-typed contingency behaviors of the male and female caregivers. A contrasting samples survey design was implemented. A random sample of 20 male caregivers who had adopted a traditionally feminine occupation was contrasted to 20 male engineers who were employed in a more traditionally masculine occupation. The male engineers were matched to the male caregivers on age, education, and years of experience. The contrasting variables were the sex-typed attitudinal preferences for boys and girls and the personality characteristics between the two groups. An additional group of 20 female caregivers matched by day care center, age, education, and experience was included to provide additional contrasts on the sex-typed attitudes and personality characteristics of the male caregivers. The sex-typed contingency behaviors of the male caregivers were also compared with those of the females

Evidence of western corn rootworm (\u3ci\u3eDiabrotica virgifera virgifera\u3c/i\u3e LeConte) field-evolved resistance to Cry3Bb1 + Cry34/ 35Ab1 maize in Nebraska

BACKGROUND: Western corn rootworm (WCR; Diabrotica virgifera virgifera) field-evolved resistance to transgenic maize expressing the Cry3Bb1 protein derived from Bacillus thuringiensis (Bt) has been confirmed across the United States Corn Belt. Although use of pyramided hybrids expressing Cry3Bb1 + Cry34/35Ab1 has increased in recent years to mitigate existing WCR Bt resistance, susceptibility of Nebraska WCR populations to this rootworm–Bt pyramid has not been assessed. Plant-based bioassays were used to characterize the susceptibility of WCR populations to Cry3Bb1 and Cry3Bb1 + Cry34/35Ab1 maize. Populations were collected from areas of northeastern Nebraska with a history of planting Bt maize that expressed Cry3Bb1 and Cry34/35Ab1. RESULTS: Significant differences in mean corrected survival among populations within Bt hybrids indicated a mosaic of WCR susceptibility to Cry3Bb1 + Cry34/35Ab1 and Cry3Bb1 maize occurred in the landscape. All field populations exhibited some level of resistance to one or both Bt hybrids when compared to susceptible laboratory control populations in bioassays. Most WCR populations exhibited incomplete resistance to Cry3Bb1 + Cry34/35Ab1 maize (92%) and complete resistance to Cry3Bb1 maize (79%). CONCLUSION: The present study confirms the first cases of field-evolved resistance to Cry3Bb1 + Cry34/35Ab1 maize in Nebraska and documents a landscape-wide WCR Cry3Bb1 resistance pattern in areas characterized by long-term continuous maize production and associated planting of Cry3Bb1 hybrids. Use of a multi-tactic integrated pest management approach is needed in areas of continuous maize production to slow or mitigate resistance evolution to Bt maize

Rats that sign-track are resistant to Pavlovian but not instrumental extinction

Individuals vary in the extent to which they attribute incentive salience to a discrete cue (conditioned stimulus; CS) that predicts reward delivery (unconditioned stimulus; US), which results in some individuals approaching and interacting with the CS (sign-trackers; STs) more than others (goal-trackers; GTs). Here we asked how periods of non-reinforcement influence conditioned responding in STs vs. GTs, in both Pavlovian and instrumental tasks. After classifying rats as STs or GTs by pairing a retractable lever (the CS) with the delivery of a food pellet (US), we introduced periods of non-reinforcement, first by simply withholding the US (i.e., extinction training; experiment 1), then by signaling alternating periods of reward (R) and non-reward (NR) within the same session (experiments 2 and 3). We also examined how alternating R and NR periods influenced instrumental responding for food (experiment 4). STs and GTs did not differ in their ability to discriminate between R and NR periods in the instrumental task. However, in Pavlovian settings STs and GTs responded to periods of non-reward very differently. Relative to STs, GTs very rapidly modified their behavior in response to periods of non-reward, showing much faster extinction and better and faster discrimination between R and NR conditions. These results highlight differences between Pavlovian and instrumental extinction learning, and suggest that if a Pavlovian CS is strongly attributed with incentive salience, as in STs, it may continue to bias attention toward it, and to facilitate persistent and relatively inflexible responding, even when it is no longer followed by reward

Interactional Structure Applied to the Identification and Generation of Visual Interactive Behavior: Robots that (Usually) Follow the Rules

Peer reviewe

Widespread but regionally specific effects of experimenter- versus self-administered morphine on dendritic spines in the nucleus accumbens, hippocampus, and neocortex of adult rats

We studied the effects of self-administered (SA) vs. experimenter-administered (EA) morphine on dendritic spines in the hippocampal formation (CA1 and dentate), nucleus accumbens shell (NAcc-s), sensory cortex (Par1 and Oc1), medial frontal cortex (Cg3), and orbital frontal cortex (AID) of rats. Animals in the SA group self-administered morphine in 2-h sessions (0.5 mg/kg/infusion, i.v.) for an average of 22 sessions and animals in the EA group were given daily i.v. injections of doses that approximated the total session dose for matched rats in Group SA (average cumulative dose/session of 7.7 mg/kg). Control rats were given daily i.v. infusions of saline. One month after the last treatment the brains were processed for Golgi-Cox staining. In most brain regions (Cg3, Oc1, NAcc-s) morphine decreased the density of dendritic spines, regardless of mode of administration (although to a significantly greater extent in Group SA). However, only SA morphine decreased spine density in the hippocampal formation and only EA morphine decreased spine density in Par1. Interestingly, in the orbital frontal cortex morphine significantly increased spine density in both Groups SA and EA, although to a much greater extent in Group SA. We conclude: 1) Morphine has persistent (at least 1 month) effects on the density of dendritic spines in many brain regions, and on many different types of cells (medium spiny neurons, pyramidal cells, and granule cells); 2) The effect of morphine on spine density (and presumably synaptic organization) varies as a function of both brain region and mode of drug administration; and 3) The ability of morphine to remodel synaptic inputs in a regionally specific manner may account for the many different long-term sequelae associated with opioid use. Synapse 46:271–279, 2002. © 2002 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34996/1/10146_ftp.pd