Methamphetamine-induced changes in the object recognition memory circuit

Abstract

Chronic methamphetamine (meth) can lead to persisting cognitive deficits in human addicts and animal models of meth addiction. Here, we examined the impact of either contingent or noncontingent meth on memory performance using an object-in-place (OIP) task, which measures the ability to detect an object relative to its location and surrounding objects. Further, we quantified monoamine transporter levels and markers of neurotoxicity within the OIP circuitry and striatum. Male Long-Evans rats received an acute meth binge (4 × 4 mg/kg i.p., 2 hour intervals) or self-administered meth (0.02 mg/infusion, i.v.; 7 days for 1 hour/day, followed by 14 days for 6 hours/day). Rats were tested for OIP recognition memory following one week of withdrawal. Subsequently, transporters for serotonin (SERT) and norepinephrine (NET) were quantified using Western blot in tissue obtained from the hippocampus, perirhinal cortex, and prefrontal cortex. In addition, striatal dopamine transporters, tyrosine hydroxylase, and glial fibrillary acidic protein were measured to assess potential neurotoxicity. Control (saline-treated) rats spent more time interacting with the objects in the changed locations. In contrast, contingent or noncontingent meth resulted in disrupted OIP performance as seen by similar amounts of time spent with all objects, regardless of location. While only acute meth binge produced signs of neurotoxicity, both meth regimens decreased SERT in the perirhinal cortex and hippocampus. Only meth self-administration resulted in a selective decrease in NET. Meth-induced changes in SERT function in the OIP circuitry may underlie memory deficits independently of overt neurotoxic effects.

The Effect of Prenatal Methamphetamine Exposure on Recognition Memory in Adult Rats

“…It is possible that MA influences more the perirhinal cortex than the hippocampus. It was proved that MA reduced transporters for serotonin in the perirhinal cortex-prefrontal cortex-hippocampal circuitry and that intact the perirhinal cortex is required for object recognition memory (Reichel et al, 2012). We can assume from our results that prenatal MA exposure can damage the perirhinal cortex and then it leads to impairment of recognition memory.…”

Dopamine Receptors and the Persistent Neurovascular Dysregulation Induced by Methamphetamine Self-Administration in Rats

“…In the same Meth self-administering rats used in the present study, we reported a progressive reduction in striatal tyrosine hydroxylase with a 50% reduction at 56 days following self-administration (Kousik et al, 2014), which is reminiscent of what is reported in human imaging studies, where Meth abusers abstinent from the drug for an average of 3 years only show a 20-30% loss in presynaptic striatal DA markers (McCann et al, 1998). Outcome differences between acute Meth treatment and self-administration may reflect differences in doses as well as the differences in the consequences of noncontingent versus contingent administration (i.e., selfadministration) (Jacobs et al, 2003;Palamarchouk et al, 2009;Reichel et al, 2012). For example, prior studies reported that Meth self-administration in rats resulted in higher levels of neurotensin (Frankel et al, 2011) and persistent reductions in DA and glutamate transmission in the NAc (Lominac et al, 2012) that were not evident in noncontingently treated rats.…”

Perirhinal Cortex mGlu5 Receptor Activation Reduces Relapse to Methamphetamine Seeking by Restoring Novelty Salience

“…This is particularly relevant given that anhedonia has been reported in psychostimulant abusers after protracted withdrawal (Leventhal et al, 2008), and persistent decreases in striatal metabolism are proposed to underlie this anhedonic state (Wang et al, 2004). Although the long-access regimen of meth self-administration employed in the present study is not expected to induce striatal toxicity per se (Reichel et al, 2012b), there may be more subtle, detrimental effects on midbrain dopamine neuron physiology that lead to diminished novelty-induced dopamine release at nucleus accumbens terminals.…”