Anterior Paralimbic Mediation of Procaine-Induced Emotional and Psychosensory Experiences

Ketter, Terence A.; Andreason, Paul; George, Mark S.; Lee, Chulhee; Gill, Debra S.; Parekh, Priti I.; Willis, Mark W.; Herscovitch, Peter; Post, Robert M.

doi:10.1001/archpsyc.1996.01830010061009

Cited by 186 publications

(106 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…in this location is supported by clinical syndromes associated with identifiable anatomic locations (Strakowski et al 1999) manifesting with emotional dysregulation, and by studies (George et al 1998;Ketter et al 1996;Mayberg et al 1999) involving healthy volunteers showing brain activation induced by mood states. Disruptions in this limbic-thalamic-prefrontal cortical circuit (Cummings 1995) may contribute to the behavioral syndromes associated with BPD.…”

Section: Discussionmentioning

confidence: 86%

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

Davanzo

2001

Neuropsychopharmacology

227

130

View full text Add to dashboard Cite

This project was designed to compare differences in brain proton spectra between children and adolescents with bipolar disorder (BPD) and gender and age-matched normal controls, and to measure changes in myo-inositol levels following lithium therapy, utilizing in vivo proton magnetic resonance spectroscopy ( 1 H MRS). A single voxel (2x2x2 cm3) was placed in brain anterior (Tondo et al. 1998). Epidemiological data (Lewinsohn et al. 1995), suggest that the prevalence of juvenile-onset BPD may be as common as rates reported in adult populations, although estimates vary widely (Costello et al. 1996). Given the increased frequency of lithium use among children and adolescents (Ryan et al. 1999) there is a clear need to assess the effects of lithium in pediatric populations. Children may have greater lithium resistance than adults (Himmelhoch and Garfinkel 1986;Hsu 1986), and it may take up to six weeks to determine, based on clinical signs and symptoms, whether a child is responding to treatment. Biological markers of treatment response would be extremely useful, particularly in these times of limited inpatient resources. The present study measured the magnetic resonance of myo-inositol and other metabolites with 1 H MRS in pediatric subjects diagnosed with BPD, before and during lithium therapy, with baseline comparison to normal controls individually matched for age and gender. We hypothesized that lithium would have an effect on the :310-825-0469, Fax: 310-206-4446, E-mail: pdavanzo@mednet.ucla.edu Received April 13, 2000; revised August 25, 2000; accepted September 14, 2000. 360 P. Davanzo et al. N EUROPSYCHOPHARMACOLOGY 2001 -VOL . 24 , NO . 4 magnetic resonance of myo-inositol in the anterior cingulate cortex in children with BPD, as measured by in vivo proton magnetic resonance spectroscopy ( 1 H MRS). Secondarily, we postulated that a decrease in myo-inositol signal in response to lithium might be a predictor of treatment efficacy.Lithium has traditionally been the preferred treatment of the manic phase of bipolar illness in adults, children (Geller and Luby 1997), and adolescents (Strober et al. 1995) with BPD. Open-label (Hsu 1986;Carlson et al. 1992;Strober et al. 1995), and one doubleblind placebo-controlled study of adolescents with substance abuse and mania (Geller et al. 1998) suggest that juveniles with BPD may have somewhat reduced benefit from acute lithium therapy compared with adults. Nevertheless, lithium continues to be widely prescribed among children and adolescents with BPD (Geller and Luby 1997) as well as for young patients presenting with excessive irritability (Fava 1997) and extreme affective dysregulation (Vitiello and Stoff 1997).The precise neurobiological mechanisms whereby lithium reduces acute manic excitement and protects against recurrence of illness remain uncertain. It is apparent that lithium exerts an effect on intracellular second-messenger systems in which activated receptorligand complexes stimulate the turnover of inositolcontaining phospholipids (del Rio et ...

show abstract

Section: Discussionmentioning

confidence: 86%

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

Davanzo

2001

Neuropsychopharmacology

227

130

View full text Add to dashboard Cite

show abstract

“…In this regard, it has been used as an affective challenge in healthy volunteers (Ketter et al, 1996;ServanSchreiber et al, 1998), and patients with mood disorders (Ketter et al, 1993) and panic disorder , as well as in individuals abusing alcohol (George et al, 1990) and cocaine (Adinoff et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…in healthy volunteers (Kellner et al, 1987), results in brief intense emotional (ranging from euphoria to dysphoria) and sensory experiences (visual, auditory, and olfactory illusions/hallucinations) in association with increased relative anterior paralimbic cerebral blood flow (CBF) as measured with [ 15 O] water positron emission tomography (PET) (Ketter et al, 1996). In healthy individuals, procaine also induces the following: hormonal changes such as increased adrenocorticotropic hormone (ACTH), cortisol, and prolactin (Kling et al, 1994); and increased temporal lobe fast activity electroencephalogram (EEG) (Parekh et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…In healthy individuals, procaine also induces the following: hormonal changes such as increased adrenocorticotropic hormone (ACTH), cortisol, and prolactin (Kling et al, 1994); and increased temporal lobe fast activity electroencephalogram (EEG) (Parekh et al, 1995). Furthermore, the right amygdala blood flow correlated with the degree of affective arousal, while the left amygdala CBF correlated positively with the degree of dysphoria and negatively with the degree of euphoria (Ketter et al, 1996). The experiences described by the subjects in these procaine studies are reminiscent of those reported after direct stimulation of limbic cortex during epilepsy surgery (Gloor et al, 1982;Halgren et al, 1978;Penfield and Jasper, 1954).…”

Section: Introductionmentioning

confidence: 99%

“…Of particular interest are the efferents of the basolateral amygdala that heavily innervate the anterior cingulate and nearby medial orbitfrontal cortex (Russchen et al, 1985). These anterior paralimbic regions with direct and indirect cholinergic connections are also the areas that exhibit the most robust activation by procaine in humans (Ketter et al, 1996). Thus, the distribution and the potential functional consequences of the cholinergic receptors in limbic pathways could allow cholinergic mechanisms to play an important role in emotion (Heimer, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Benson

Carson

Kiesewetter

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([ 18 F]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M 2 ) receptors. On separate days each animal received six different doses of i.v. procaine in a randomized fashion. Procaine blocked up to B90% of [ 18 F]FP-TZTP specific binding globally in a dose-related manner. There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC 50 ) for [ 18 F]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC 50 for average cortex. Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M 2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion.

show abstract

Effects of Intrathecal Thyrotropin-Releasing Hormone (Protirelin) in Refractory Depressed Patients

Marangell

George²,

Callahan³

et al. 1997

Arch Gen Psychiatry

109

View full text Add to dashboard Cite

show abstract

Anterior Paralimbic Mediation of Procaine-Induced Emotional and Psychosensory Experiences

Abstract: Procaine increased anterior paralimbic CBF, and different clinical responses appeared to be associated with different patterns of CBF changes.

Cited by 186 publications

References 64 publications

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Effects of Intrathecal Thyrotropin-Releasing Hormone (Protirelin) in Refractory Depressed Patients

Contact Info

Product

Resources

About