Publications by authors named "Gopi A Tejwani"

5 Publications

  • Page 1 of 1

Acute nicotine changes dynorphin and prodynorphin mRNA in the striatum.

Psychopharmacology (Berl) 2009 Jan 21;201(4):507-16. Epub 2008 Sep 21.

Department of Psychiatry, College of Medicine, Ohio State University, Columbus, OH 43210, USA.

Rationale: Nicotine displays rewarding and aversive effects, and while dopamine has been linked with nicotine's reward, the neurotransmitter(s) involved with aversion remains speculative. The kappa-dynorphinergic system has been associated with negative motivational and affective states, and whether dynorphin (Dyn) contributes to the behavioral pharmacology of nicotine is a pertinent question.

Objective: We determined whether administration of a single dose of nicotine alters the biosynthesis of Dyn in the striatum of mice.

Results: Nicotine free base, 1 mg/kg, sc, induced a biphasic, protracted increase of striatal Dyn, an initial rise by 1 h, which declined to control levels by 2 h, and a subsequent increase, between 6 and 12 h, lasting over 24 h. At 1 h, the nicotine effect was dose dependent, with doses>or=0.5 mg/kg inducing a response. Prodynorphin mRNA increased by 30 min for over 24 h, and in situ hybridization demonstrated elevated signal in caudate/putamen and nucleus accumbens. The nicotinic antagonist mecamylamine prevented the Dyn response, and a similar effect was observed with D1- and D2-like dopamine receptor antagonists, SCH 23390, sulpiride, and haloperidol. The glutamate NMDA receptor antagonist MK-801 reversed the nicotine-induced increase of Dyn, while the AMPA antagonist NBQX had a marginal effect.

Conclusions: We interpret our findings to indicate that acute nicotine enhances the synthesis and release of striatal Dyn. We propose that nicotine influences Dyn primarily through dopamine release and that glutamate plays a modulatory role. A heightened dynorphinergic tone may contribute to the aversive effects of nicotine in naive animals and first-time tobacco smokers.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
January 2009

Dynorphin and prodynorphin mRNA changes in the striatum during nicotine withdrawal.

Synapse 2008 Jun;62(6):448-55

Department of Psychiatry, College of Medicine, Ohio State University, Columbus, Ohio 43210, USA.

Nicotine withdrawal causes somatic and negative affective symptoms that contribute to relapse and continued tobacco smoking. So far, the neuronal substrates involved are not fully understood, and an opioid role has been suggested. In this regard, the opioid dynorphin (Dyn) is of interest as it produces aversive states and has been speculated to play a role in the nicotine behavioral syndrome. These studies explore whether Dyn metabolism is altered during withdrawal following chronic administration of nicotine. Mice were administered nicotine, 2 mg/kg, s.c., four times daily for 14 days, and Dyn and prodynorphin (PD) mRNA estimated in selective brain regions at various times (30 min to 96 h) following drug discontinuation. The content of Dyn, estimated by RIA, was decreased in the striatum for a protracted time, from 30 min to over 72 h. In contrast, the mRNA for PD, evaluated by Northern blot, was elevated, appearing by 8 h and lasting over 96 h. Dyn was decreased in both ventral and dorsal striatum, and PD mRNA was differentially increased in the two striatal compartments as demonstrated by in situ hybridization. PD message was predominantly augmented in the nucleus accumbens, rostral pole, core, and shell, and the medial aspects of caudate/putamen. We interpret these data to indicate increased activity of striatal, particularly accumbal, dynorphinergic neurons during nicotine withdrawal resulting in enhanced peptide release and compensatory synthesis. Heightened dynorphinergic tone might be responsible, in part, for the emergence of the negative affective states observed during nicotine withdrawal.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
June 2008

Cutaneous analgesia, hemodynamic and respiratory effects, and beta-endorphin concentration in spinal fluid and plasma of horses after acupuncture and electroacupuncture.

Am J Vet Res 2002 Oct;63(10):1435-42

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.

Objective: To determine cutaneous analgesia, hemodynamic and respiratory effects, and beta-endorphin concentration in spinal fluid and plasma of horses after acupuncture and electroacupuncture (EA).

Animals: 8 healthy 10- to 20-year-old mares that weighed between 470 and 600 kg.

Procedure: Each horse received 2 hours of acupuncture and 2 hours of PAES at acupoints Bladder 18, 23, 25, and 28 on both sides of the vertebral column as well as sham needle placement (control treatment). Each treatment was administered in a random order. At least 7 days elapsed between treatments. Nociceptive cutaneous pain threshold was measured by use of skin twitch reflex latency (STRL) and avoidance to radiant heat (< or = 50 degrees C) in the lumbar area. Skin temperature, cardiovascular and respiratory variables, and beta-endorphin concentration in spinal fluid (CSF-EN) and plasma (plasma-EN) were measured.

Results: Acupuncture and PAES significantly increased STRL and skin temperature. The CSF-EN was significantly increased from baseline values 30 to 120 minutes after onset of PAES, but it did not change after acupuncture and control treatments. Heart and respiratory rates, rectal temperature, arterial blood pressure, Hct, total solids and bicarbonate concentrations, base excess, plasma-EN, and results of blood gas analyses were not significantly different from baseline values after acupuncture, PAES, and control treatments.

Conclusions And Clinical Relevance: Administration of PAES was more effective than acupuncture for activating the spinal cord to release beta-endorphins into the CSF of horses. Acupuncture and PAES provided cutaneous analgesia in horses without adverse cardiovascular and respiratory effects.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
October 2002

The role of spinal opioid receptors in antinociceptive effects produced by intrathecal administration of hydromorphone and buprenorphine in the rat.

Anesth Analg 2002 Jun;94(6):1542-6, table of contents

Department of Pharmacology, College of Medicine and Public Health, Ohio State University, 5197 Graves Hall, 333 W 10th Avenue, Columbus, OH 43210-1239, USA.

Unlabelled: The intrathecal administration of morphine has been the standard therapy to control long-term intractable pain. Recently, a panel of pain therapy experts suggested that because of the lack of efficacy or because of the side effects produced by morphine in some patients, other drugs, such as hydromorphone and buprenorphine, should be investigated for their analgesic properties. We designed this study to compare the efficacy of intrathecal hydromorphone and buprenorphine to suppress thermal nociception in male Sprague-Dawley rats. An additional objective was to understand whether hydromorphone and buprenorphine bind and act as agonists to mu-, delta-, and kappa-spinal opioid receptors. Intrathecally-administered hydromorphone and buprenorphine produced a dose- and time-dependent increase in the tail-flick response latency in rats. The 50% effective dose value for the antinociceptive effect of buprenorphine and hydromorphone were 4 and 69.5 nmol/L, respectively. Both drugs act as agonists to mu-opioid receptors, as determined by their ability to displace [(3)H]-DAMGO from the spinal opioid receptors and by the ability of an opioid receptor antagonist, naloxone, to reverse their antinociceptive effects. Buprenorphine also has an agonistic effect on the kappa-opioid receptors. For the first time, we report that intrathecal buprenorphine is approximately 17 times more effective than hydromorphone in inhibiting thermal pain, and buprenorphine produces its antinociceptive effect by acting as an agonist at both mu- and kappa-spinal opioid receptors. Naloxone administered intrathecally was effective in preventing the antinociceptive effects of subsequent intrathecal injections of buprenorphine.

Implications: Hydromorphone and buprenorphine are two important drugs used for pain relief. We observed that intrathecal buprenorphine is 17 times more potent than hydromorphone to inhibit pain in rats. Both drugs exert their effects through specific spinal opioid receptors.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
June 2002

Met-enkephalin and preproenkephalin mRNA changes in the striatum of the nicotine abstinence mouse.

Neurosci Lett 2002 May;325(1):67-71

Department of Psychiatry, The Ohio State University School of Medicine and Public Health, 5034 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.

We studied the changes of met-enkephalin (Met-Enk) content and preproenkephalin (PPE) mRNA in the striatum in a mouse model of nicotine abstinence. Nicotine, 2 mg/kg, s.c., was administered four times daily for 14 days and Met-Enk and PPE mRNA evaluated at various times (4-96 h) following drug discontinuation. Met-Enk, assayed by radioimmunoassay, was increased in the ventral (nucleus accumbens) but not dorsal (putamen/caudate) striatum, while PPE mRNA, assayed in whole striatum by Northern blotting was elevated. Both changes were seen early during withdrawal and lasted over 72 h. In situ hybridization revealed enhanced signal in the dorsal striatum, mostly laterally, and smaller increases in the rostral pole, core and shell of the nucleus accumbens. These observations indicate that during nicotine withdrawal, striatal enkephalinergic neurons undergo adaptative responses, which might contribute to the abstinence behavioral syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
May 2002