dizocilpine-maleate and 4-carboxyphenylglycine

To examine the relationship between glutamate receptors and the action of NC-1900 on a step-through passive avoidance (PA) task in mice, MK-801, an NMDA receptor blocker, and (S)-4-carboxyphenylglycine (4CPG), a group I metabotropic receptor antagonist, were administered intraventricularly (i.c.v.) singly or as co-injections. The i.c.v. injection of MK-801 (0.8 microg) or 4CPG (2 microg) decreased the latency on the PA task. NC-1900 (1 ng/kg, subcutaneously (s.c.)) alone prolonged the latency on the retention trial in the PA task. MK-801 (0.2 and 0.8 microg) or 4CPG (0.5 and 2 microg) significantly inhibited the action of NC-1900, while the s.c. injection of NC-1900 did not affect latency in mice that received i.c.v. co-injection of MK-801 and 4CPG at any of the doses tested. These results suggest that glutamate receptors participate in the action of NC-1900 on learning and memory in PA task performance.

Topics: Animals; Avoidance Learning; Benzoates; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Glutamic Acid; Glycine; Male; Memory; Mice; N-Methylaspartate; Oligopeptides; Pyrrolidonecarboxylic Acid; Receptors, Glutamate; Vasopressins

The present study examined the effects of intrathecal (i.t.) treatment (twice-daily injections on post-operative (PO) days 0-8) with the metabotropic glutamate receptor (mGluR) compound, (S)-4-carboxyphenylglycine ((S)-4CPG), or the non-competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilipine maleate (MK-801), on mechanical allodynia and cold hyperalgesia associated with chronic constriction injury (CCI) of the sciatic nerve in rats. Also, the effects of early (twice-daily injections on days 0-3) or late (twice-daily injections on days 8-11) (S)-4CPG treatment on the injury-related mechanical allodynia and cold hyperalgesia were assessed in CCI rats. Results demonstrated that 8-day (S)-4CPG or MK-801 treatment attenuated mechanical allodynia (up to PO days 12 or 16, respectively) and cold hyperalgesia (up to PO days 8 or 16, respectively). Results also demonstrated that early (S)-4CPG treatment significantly attenuated the development of mechanical allodynia (90 and 270 nmol) and cold hyperalgesia (270 nmol). However, late treatment with (S)-4CPG did not reduce the nociceptive behaviours in either behavioural task. These data not only confirm that the NMDA receptor plays a role in chronic nociception, but also suggest that Group I mGluRs are more critically involved in the development, and not the maintenance, of mechanical allodynia and cold hyperalgesia associated with CCI in rats.

Topics: Animals; Benzoates; Cold Temperature; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Glycine; Hyperalgesia; Injections, Spinal; Male; Nerve Compression Syndromes; Physical Stimulation; Rats; Rats, Inbred Strains; Sciatic Nerve; Time Factors

1. The contribution of various excitatory amino acid (EAA) receptors (NMDA, AMPA/kainate and metabotropic) in the brain to the development of morphine dependence was examined. This was performed by measuring the severity of the precipitated withdrawal syndrome following chronic subcutaneous (s.c.) morphine and intracerebroventricular (i.c.v.) EAA antagonist treatment. 2. Continuous subcutaneous (s.c.) treatment with morphine sulphate (36.65 mumol day-1) produced an intense and reliable naloxone-precipitated withdrawal syndrome. 3. Chronic i.c.v. treatment with antagonists selective for metabotropic and NMDA receptors, but not AMPA/kainate receptors, significantly attenuated abstinence symptoms. Conversely, EAA antagonists had very little effect on non-withdrawal behaviours. 4. These results suggest that, as well as changes elicited by activation of NMDA receptors, metabotropic receptors and intracellular changes in the phosphatidylinositol (PI) second-messenger system or the cyclic adenosine 3',5'-monophosphate (cAMP) second messenger system, to which EAA metabotropic receptors are linked, may be involved in the development of opioid dependence with chronic morphine treatment.

Topics: Alanine; Animals; Anti-Anxiety Agents; Behavior, Animal; Benzoates; Benzodiazepines; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glycine; Injections, Intraventricular; Injections, Subcutaneous; Male; Morphine; Morphine Dependence; Rats; Receptors, AMPA; Receptors, Kainic Acid; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome