Biomedical subjects

Kerry J Ressler

Publications and source records attributed to Kerry J Ressler.

23 records · Page 2Linked to original sources

PubMed2004

Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment.

Recent postmortem studies in humans suggest that defects in GABAergic neurotransmission might contribute to the neuropathology associated with schizophrenia. Disturbances in GABAergic systems may also contribute to the sensorimotor gating deficits classically observed in schizophrenic patients, including deficits in prepulse inhibition (PPI). To explore the relationship, the current study examined the integrity of PPI and startle habituation in knockout (KO) mice that lack the GABA synthesizing enzyme glutamic acid decarboxylase 65 (GAD 65). GAD65 KO mice displayed normal baseline and habituated startle responses, which did not differ from GAD65 wild-type (WT) or heterozygous (HET) mice. However, GAD65 KO mice showed robust deficits in PPI which were reversed by the atypical antipsychotic agent clozapine. These results lend support to the view that abnormalities in GABAergic systems might contribute to the basic pathophysiological mechanisms in schizophrenia.

Acoustic Stimulation↗

PubMed2002

Regulation of synaptic plasticity genes during consolidation of fear conditioning.

In mammals, long-term memory induced by Pavlovian fear conditioning has been shown to be dependent on the amygdala during a protein and mRNA synthesis-dependent phase of memory consolidation. We have used genes identified in a kainic acid model of synaptic plasticity as in situ hybridization probes during the consolidation period after fear conditioning. We found that these genes were transcriptionally regulated in several brain areas only when stimuli were presented in a manner that supported behavioral learning and not after unpaired presentations or footshocks alone. Immediate early genes and neurofilament mRNA peaked approximately 30 min after conditioning, as expected. Interestingly, nurr-1, alpha-actinin, and 16c8 increased approximately 2-4 hr later, whereas neurogranin and gephyrin decreased during that time. Our results suggest that fear memory consolidation occurs within a broad neural circuit that includes, but is not limited to, the amygdala. Together, a broad array of transcriptionally regulated genes, encoding transcription factors, cytoskeletal proteins, adhesion molecules, and receptor stabilization molecules, appear to mediate the neural plasticity underlying specific forms of long-term memory in mammals.

Animals↗

PubMed2002

Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats.

NMDA receptor antagonists block conditioned fear extinction when injected systemically and also when infused directly into the amygdala. Here we evaluate the ability of D-cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine-recognition site on the NMDA receptor complex, to facilitate conditioned fear extinction after systemic administration or intra-amygdala infusions. Rats received 10 pairings of a 3.7 sec light and a 0.4 mA footshock (fear conditioning). Fear-potentiated startle (increased startle in the presence vs the absence of the light) was subsequently measured before and after 30, 60, or 90 presentations of the light without shock (extinction training). Thirty non-reinforced light presentations produced modest extinction, and 60 or 90 presentations produced nearly complete extinction (experiment 1). DCS injections (3.25, 15, or 30 mg/kg) before 30 non-reinforced light exposures dose-dependently enhanced extinction (experiment 2) but did not influence fear-potentiated startle in rats that did not receive extinction training (experiment 3). These effects were blocked by HA-966, an antagonist at the glycine-recognition site (experiment 4). Neither DCS nor HA-966 altered fear-potentiated startle when injected before testing (experiment 5). The effect of systemic administration was mimicked by intra-amygdala DCS (10 microg/side) infusions (experiment 6). These results indicate that treatments that promote NMDA receptor activity after either systemic or intra-amygdala administration promote the extinction of conditioned fear.

Acoustic Stimulation↗

PubMedDate not supplied

Different mechanisms of fear extinction dependent on length of time since fear acquisition.

Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and unsignaled presentations of the unconditioned stimulus (reinstatement). However, there also is evidence to suggest that extinction is an "unlearning" process corresponding to depotentiation of potentiated synapses within the amygdala. Because depotentiation is induced more readily at short intervals following LTP induction and is not inducible at all at a sufficient delay, it may be that extinction initiated shortly following fear acquisition preferentially engages depotentiation/"unlearning," whereas extinction initiated at longer delays recruits a different mechanism. We investigated this possibility through a series of behavioral experiments examining the recoverability of conditioned fear following extinction. Consistent with an inhibitory learning mechanism of extinction, rats extinguished 24-72 h following acquisition exhibited moderate to strong reinstatement, renewal, and spontaneous recovery. In contrast, and consistent with an erasure mechanism, rats extinguished 10 min to 1 h after acquisition exhibited little or no reinstatement, renewal, or spontaneous recovery. These data support a model in which different neural mechanisms are recruited depending on the temporal delay of fear extinction.

Animals↗

PubMedDate not supplied

Pain medication use among patients with posttraumatic stress disorder.

The relationship of analgesic medication use with posttraumatic stress disorder (PTSD) diagnosis was investigated among a sample of 173 African Americans presenting for routine outpatient visits at an urban mental health center. Seventy-eight (43.5%) of the sample met DSM-IV PTSD criteria. Those with PTSD had significantly higher use of analgesic medication (both opiate and non-opiate), as compared with non-PTSD patients. PTSD symptoms, as measured by the Posttraumatic Symptom Scale, were significantly higher in subjects who were prescribed analgesics. The authors conclude that there may be a relationship between PTSD and use of pain medications warranting further examination of the endogenous opiate system in the pathophysiology of PTSD.

Adult↗