A selective phosphodiesterase IV inhibitor, rolipram blocks both withdrawal behavioral manifestations, and c-Fos protein expression in morphine dependent mice

Hamdy, Moustafa Mahmoud; Mamiya, Takayoshi; Noda, Yukihiro; Sayed, Merfat; Assi, Abdel Azim; Gomaa, Adel A.; Yamada, Kiyofumi; Nabeshima, Toshitaka

doi:10.1016/s0166-4328(00)00315-6

Cited by 30 publications

(17 citation statements)

References 36 publications

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“…For instance, AV411 may have been ameliorating effects of methamphetamine abstinence which was supporting continued drug-seeking. Consistent with this possibility are reports that AV411 (Hutchinson et al, 2009; Ledeboer et al, 2007), as well as drugs which overlap its pharmacology (Hamdy et al, 2001; Mamiya et al, 2001), can attenuate withdrawal effects of the opiates. Another possibility is that AV411 nonspecifically suppressed responding.…”

Section: Discussionmentioning

confidence: 79%

The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse

Beardsley

Shelton

Hendrick

et al. 2010

European Journal of Pharmacology

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Stress and renewed contact with drug (a “slip”) have been linked to persisting relapse of methamphetamine abuse. Human brain microglial activation has been linked with methamphetamine abuse, and inhibitors of glial cell activation, certain phosphodiesterase (PDE) inhibitors, and glial cell derived neurotrophic factor (GDNF) have been reported to modulate drug abuse effects. Our objective was to determine whether the glial cell attenuator, 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine (AV411, ibudilast), a non-selective PDE inhibitor and promoter of GDNF, could reduce stress- and methamphetamine prime-induced reinstatement of methamphetamine-seeking behavior. Male Long-Evans hooded rats were trained to lever press reinforced with 0.1 mg/kg i.v. methamphetamine infusion according to fixed-ratio 1 (FR1) reinforcement schedules during daily, 2-h experimental sessions. After performance had stabilized, lever pressing was extinguished for 12 consecutive sessions and doses of 0 (vehicle), 2.5 and 7.5 mg/kg AV411 were then administered intraperitoneally b.i.d. on the last two days of extinction and then once on the testday to separate groups of 12 rats. During testing, the rats were given 15 min of intermittent footshock or a 1 mg/kg i.p. methamphetamine prime followed by a 2-h reinstatement test session. AV411 significantly reduced response levels of footshock-induced (2.5 and 7.5 mg/kg) and prime-induced (7.5 mg/kg) reinstatement of extinguished methamphetamine-maintained responding. AV411 has properties consistent with the ability to attenuate relapse precipitated by stress and methamphetamine “slips” during abstinence. These results thus reinforce interest in atypical neurobiological mechanisms which could be exploited for developing novel medications for treating drug abuse disorders.

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Section: Discussionmentioning

confidence: 79%

The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse

Beardsley

Shelton

Hendrick

et al. 2010

European Journal of Pharmacology

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“…For example, coadministration of rolipram, a specific PDE4 inhibitor, reduced naloxone-precipitated morphine withdrawal (Hamdy et al, 2001; Mamiya et al, 2001). PDE4 inhibitor, pentoxifyllin reduced expression of the microglial activation marker CD11b/c and reduced behavioral tolerance in morphine-tolerant mice, suggesting that the behavioral effects of pentoxifyllin on morphine tolerance involve microglia (Mika et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release

Bland

Hutchinson

Maier

et al. 2009

Brain, Behavior, and Immunity

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Glial activation has recently been discovered to modulate several effects of morphine, including analgesia, tolerance, and dependence. The present studies extend this line of investigation by exploring whether glial activation may also affect extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) shell, a neurochemical corollary of morphine-induced drug reward, during a challenge dose of morphine in experiments both with and without precipitated withdrawal. Morphine or vehicle was administered s.c. for 4 days (starting at 15 mg/kg/day up to 20 mg/kg/day), and the glial activation inhibitor AV411 (7.5 mg/kg) or vehicle was administered twice daily. A challenge dose of morphine (22.5 mg/kg) or saline was then given during dialysis. In the first experiment, naloxone (10 mg/kg) was administered 1 hr after morphine during dialysis in AV411-or vehicle-treated rats, and behavioral signs of somatic withdrawal were assessed during microdialysis. In the second experiment, using the same dosing regimen, sampling continued 3 hr after morphine or saline in AV411-or vehicle-treated rats. NAc DA increased in vehicle-treated rats significantly more than in AV411-treated rats before naloxone treatment, and withdrawal symptoms were significantly reduced in AV411-treated rats. The decrease in morphine-induced NAc DA by AV411 was persistent, lasting 3+ hr post-morphine. These results indicate that glial activation contributes to the effects of morphine on NAc DA, which is associated with somatic signs of precipitated withdrawal.

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“…This effect probably occurs via increase of cAMP levels at dopamine D 2 -receptors (46). In addition, rolipram reduces morphine withdrawal symptoms probably via decrease of c-Fos expression (28). This article will review the pharmacology, toxicology, and clinical effects on the CNS and the immune system.…”

Section: Introductionmentioning

confidence: 99%

The Antidepressant and Antiinflammatory Effects of Rolipram in the Central Nervous System

2001

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Rolipram is a selective inhibitor of phosphodiesterases (PDE) IV, especially of the subtype PDE IVB. These phosphodiesterases are responsible for hydrolysis of the cyclic nucleotides cAMP and cGMP, particularly in nerve and immune cells. Consequences of rolipram-induced elevation of intracellular cAMP are increased synthesis and release of norepinephrine, which enhance central noradrenergic transmission, and suppress expression of proinflammatory cytokines and other mediators of inflammation. In humans and animals rolipram produces thereby a variety of biological effects. These effects include attenuation of endogenous depression and inflammation in the central nervous system (CNS), both effects are of potential clinical relevance. There are some discrepancies between in vitro and in vivo effects of rolipram, as well as between results obtained in animal models and clinical studies. The clinical use of rolipram is limited because of its behavioral and other side effects. Newly developed selective PDE IV inhibitors with presumably higher potency and lower toxicity are currently under investigation.

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A selective phosphodiesterase IV inhibitor, rolipram blocks both withdrawal behavioral manifestations, and c-Fos protein expression in morphine dependent mice

Cited by 30 publications

References 36 publications

The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse

The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse

The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release

The Antidepressant and Antiinflammatory Effects of Rolipram in the Central Nervous System

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