Meg Waraczynski

Panic attack symptomatology and anxiety sensitivity in adolescents

The relationship between panic attack symptoms, anxiety sensitivity, and academic performance was evaluated in a sample of 77 high school students. Although it has been suggested that children and adolescents are unlikely to experience panic attacks and panic disorder, the results of recent studies suggest that symptoms frequently occur in this age group. Evaluation of symptoms reported on the Panic Attack Questionnaire revealed that 39% of our sample experienced panic attacks, and that five subjects (6.5%) met diagnostic criteria for panic disorder at some time during their life. Furthermore, a significant correlation between scoring on the PAQ and scores on the Childhood Anxiety Sensitivity Index, a fear of anxiety measure, was found. Results suggest that there is a relationship between anxiety sensitivity and panic symptomatology in adolescents, a finding comparable with the adult literature. The observed relationship between anxiety sensitivity and panic symptomatology in adolescents is congruent with theorizing that anxiety sensitivity is a cognitive risk factor for the development of panic disorder.

Temporary inactivation of the retrorubral fields decreases the rewarding effect of medial forebrain bundle stimulation

Prior studies indicate that lesioning the retrorubral fields (RRF) decreases the rewarding effect of medial forebrain bundle (MFB) stimulation, although these studies did not make the RRF their primary target. This study directly investigates the role of the RRF in MFB self-stimulation using transient lidocaine-induced inactivation of target tissue rather than permanent lesioning. In 18 rats with MFB stimulation electrodes, inactivation of the RRF via 0. 5 and 1.0 microl of 4% lidocaine produced immediate, substantial upward shifts in the frequency required to maintain half-maximal self-stimulation response rates whereas injecting comparable volumes of saline did not. Bilateral inactivation was particularly effective, especially at medium and high stimulation currents, although unilateral inactivation ipsilateral to the stimulation site was also effective. Contralateral inactivation alone did not substantially change the stimulations reward value, although contralateral inactivation appeared to contribute to the effectiveness of bilateral inactivation. The frequency required to maintain half-maximal responding returned to baseline levels by 15-20 min after lidocaine infusion. In seven rats whose infusion sites were not in the RRF, lidocaine inactivation did not consistently degrade the stimulations reward value. These results indicate that some neural elements located in the RRF contribute to the rewarding effect of MFB stimulation. Possible roles for these elements in the anatomical substrate for MFB self-stimulation are discussed.

Lidocaine inactivation demonstrates a stronger role for central versus medial extended amygdala in medial forebrain bundle self-stimulation.

Given recent attention to the role of the extended amygdala (EA) in brain reward processes, this study examines the relative contributions of the medial versus central aspects of that forebrain macrostructure to the rewarding effects of medial forebrain bundle (MFB) stimulation. Thirty-one rats were self-stimulated at either the rostral or caudal MFB before and after lidocaine-induced inactivation of an EA target. Relative to non-injection baseline tests, the injection of 0.5 or 1.0 microl of 4% lidocaine into the central EA structures of the lateral bed nucleus of the stria terminalis, the central sublenticular EA, and the interstitial nucleus of the posterior limb of the anterior commissure frequently and substantially disrupted the rewarding effect of MFB stimulation, whereas comparable saline infusions did not. The effects were most pronounced when the central EA was inactivated either bilaterally or ipsilateral to the stimulation site. Contralateral inactivation was less effective but did impair the stimulations reward effects in several cases. Inactivation of medial EA structures did not have as great or as consistent effects on stimulation reward value except when the lidocaine infusion encroached on the MFB itself. These results support prior demonstrations of the EAs role in brain reward and motivational processes and further show that the central rather than medial aspects of the EA are particularly relevant. The results are discussed in the context of possible anatomical substrates supporting MFB self-stimulation.

Brain stimulation reward is affected by D2 dopamine receptor manipulations in the extended amygdala but not the nucleus accumbens

This work examines the effects on brain stimulation reward (BSR) of D1 and D2 dopamine receptor manipulations in the sublenticular central extended amygdala (SLEAc) and the nucleus accumbens shell (NAc). Fifty-three male Long Evans rats received medial forebrain bundle stimulation electrodes and bilateral injection guide cannulae aimed at either the SLEAc or the NAc. The rate-frequency paradigm was used to assess drug-induced changes in stimulation reward effectiveness and in response rate following 0.50 microl injections of isotonic saline, 5.0mug of SKF38393 (D1 receptor agonist), 2.0 microg of SCH 23390 (D1 blocker), 10.0 microg of quinpirole (D2 agonist) and 3.0 microg of eticlopride (D2 blocker). The drugs were injected both ipsi- and contralateral to the stimulation site. When injected into the NAc none of the drugs affected either the frequency required to maintain half-maximal responding or maximum response rate. D2 receptor blockade in the SLEAc contralateral to the stimulation site significantly but modestly enhanced both the stimulations reward effectiveness and response rate while D2 receptor agonism decreased responding. Injections into the SLEAc ipsilateral to the stimulation site were ineffective. These results suggest that dopaminergic neurotransmission in the SLEAc is more important to reward processes than is dopamine in the NAc. We align our findings with past work by considering methodological details and a currently hypothesized role for NAc dopamine in learning behaviors that lead to reward capture.

Lesions and inactivation implicate dorsolateral hindbrain in MFB self-stimulation

Two experiments explored the role of the motor nucleus of the trigeminal nerve (Mo5) and surrounding area in the rewarding effects of medial forebrain bundle (MFB) stimulation. In the first, eight rats received serial bilateral lesions of the target region. The reward value of MFB stimulation was assessed at 200, 400, and 800 microA using the rate-frequency curve shift paradigm. In five rats, no lesions affecting the motor nucleus or its surrounding area affected the frequency required to maintain half-maximal response rate at any current. One rat with a relatively ventrally placed lesion showed substantial enhancement of stimulation reward value at two currents, while two rats with lesions affecting the area around the descending fibers of the superior cerebellar peduncle (scp) showed substantial increases in required frequency. In the second experiment, six rats received uni- and bilateral injections of lidocaine to temporarily inactivate the target area. Two rats with injections centered near the descending fibers of the scp showed substantial increases in required frequency, as great as 0.30 log(10) units. Two rats with injections slightly rostral to these showed little change in required frequency. Two rats with injections in the ventral cerebellum, just lateral to the fastigial nucleus, showed increases in required frequency, particularly following injections contralateral to the MFB stimulation site. These data are interpreted to imply a role for the area around the lateral pole of the scp, perhaps including axons arising from the cerebellum, in MFB stimulation reward.

Midbrain periaqueductal lesions do not degrade medial forebrain bundle stimulation reward.

To investigate the possible role of the midbrain central grey and dorsal raphe in medial forebrain bundle (MFB) self-stimulation, 12 rats received monopolar stimulation electrodes in both the lateral hypothalamic and ventral tegmental MFB and an ipsilateral lesioning electrode in either the central grey or dorsal raphe. Baseline rate-frequency data were collected at several currents at each stimulation site until the frequency required to maintain half-maximal responding stabilized and then an electrolytic lesion was made by passing either 20 or 60 s of anodal constant current through the lesioning electrode. Post-lesion rate-frequency data indicated that lesions of the central grey and dorsal raphe had little appreciable effect on the rewarding nature of MFB stimulation. One rats lesion damaged the median raphe and produced sustained downward shifts in required frequency, suggesting post-lesion enhancement of the stimulations rewarding effect.

Lesions of midline midbrain structures leave medial forebrain bundle self-stimulation intact

Previous work with psychophysically-based collision methods and pharmacological manipulation suggests a role in medial forebrain bundle (MFB) self-stimulation for neurons lying along the midline between the cerebral hemispheres, in the mid- and/or hindbrain. Also, recently-proposed models of the anatomical substrate for medial forebrain bundle stimulation reward suggest that at least part of the directly-activated axons of this substrate arise from mid- and/or hindbrain somata, bifurcate, and send bilateral projections to the MFB of each hemisphere. Branches of these axons are thought to cross the midline at some point near the ventral tegmental area. This study examines the effects on MFB stimulation reward of lesioning midbrain structures that lie along the midline between hemispheres. In 13 rats, lesions of the median raphe, the decussation of the superior cerebellar peduncle, or the interpeduncular nucleus were all ineffective in altering the stimulation frequency required to maintain half-maximal levels of operant responding for stimulation reward. These results are discussed in terms of implications for recent models of the anatomical substrate for brain stimulation reward.

Brain stimulation reward is altered by affecting dopamine–glutamate interactions in the central extended amygdala

This work compares the effects on brain stimulation reward (BSR) when combining D2 dopamine receptor and AMPA glutamate receptor manipulations in the sublenticular central extended amygdala (SLEAc) and the nucleus accumbens shell (NAc shell). Thirty-seven male Long Evans rats received medial forebrain bundle (MFB) stimulation electrodes and bilateral injection guide cannulae aimed at either the SLEAc or the NAc shell. The rate-frequency paradigm was used to assess drug-induced changes in stimulation reward effectiveness and in response rate following 0.5 μl infusions of 0.50 μg of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) (AMPA receptor antagonist), 10.0 μg of quinpirole (D2 receptor agonist), 0.25 μg of AMPA (AMPA receptor agonist), 3.0 μg of eticlopride (D2 receptor antagonist), 0.50 μg of NBQX with 10.0 μg of quinpirole, and 0.25 μg of AMPA with 3.0 μg of eticlopride. The drugs were injected both ipsi- and contralateral to the stimulation site. AMPA blockade and D2 stimulation synergized to reduce BSRs reward efficacy when directed at the SLEAc contralateral to the stimulation site whereas changes in reward efficacy were primarily D2-dependent following injections into the ipsilateral SLEAc. When injected into the NAc shell the drugs had only one significant effect on the frequency required to maintain half-maximal responding: injections of NBQX with quinpirole ipsilateral to the stimulation site increased required frequency significantly more than did injections of saline. Contrary to expectations, stimulating AMPA receptors with and without co-blockade of D2 receptors also decreased the stimulations reward efficacy, although these effects may reflect general behavioral disruption more than effects on reward per se. These results indicate a role for the SLEAc in BSR and also suggest that SLEAc neurons ipsi- and contralateral to the stimulated MFB play their roles in BSR through different mechanisms.

Toward a systems-oriented approach to the role of the extended amygdala in adaptive responding.

Research into the structure and function of the basal forebrain macrostructure called the extended amygdala (EA) has recently seen considerable growth. This paper reviews that work, with the objectives of identifying underlying themes and developing a common goal towards which investigators of EA function might work. The paper begins with a brief review of the structure and the ontological and phylogenetic origins of the EA. It continues with a review of research into the role of the EA in both aversive and appetitive states, noting that these two seemingly disparate avenues of research converge on the concept of reinforcement - either negative or positive - of adaptive responding. These reviews lead to a proposal as to where the EA may fit in the organization of the basal forebrain, and an invitation to investigators to place their findings in a unifying conceptual framework of the EA as a collection of neural ensembles that mediate adaptive responding.

Comparison of the effects on brain stimulation reward of D1 blockade or D2 stimulation combined with AMPA blockade in the extended amygdala and nucleus accumbens

This report compares the effects on medial forebrain bundle self-stimulation of injecting into either the sublenticular central extended amygdala (SLEAc) or nucleus accumbens shell (NAcS) the D1 dopamine receptor blocker SCH23390 or the D2 dopamine receptor agonist quinpirole alone or in combination with the AMPA glutamate receptor blocker NBQX. These manipulations all render affected neurons less excitable and therefore are expected to increase the stimulation pulse frequency required to maintain half-maximal response rate (required frequency, or RF). Injections were made ipsilateral and contralateral to the stimulation site but not bilaterally. Injecting quinpirole alone or in combination with NBQX was more effective in increasing RF than was injecting SCH23390 either alone or with NBQX. Quinpirole alone and in combination with NBQX was more effective when injected into the SLEAc than into the NAcS, and the combination injection was more effective than quinpirole alone, especially when injected into the SLEAc contralateral to the stimulation site. Maximum response rates were only modestly decreased by any drug injection. These data suggest a stronger role in brain stimulation reward for D2/glutamate than D1/glutamate interactions in the extended amygdala.