Essential role of D1 but not D2 receptors in methamphetamine‐induced impairment of long‐term potentiation in hippocampal–prefrontal cortex pathway

Abstract

Methamphetamine (MA) abuse induces deficits in cognitive performance that are related to dysfunction of the prefrontal cortex (PFC). The medial portion of the prefrontal cortex (mPFC) in rats that is crucial for cognitive function has been shown to undergo long-term potentiation (LTP) in the projections from the hippocampus. However, no study has been performed to evaluate the influence of MA on synaptic plasticity in the hippocampal-mPFC pathways. In the present experiments, we investigated the effects of repeated MA administration on hippocampal-mPFC LTP, together with MA-induced stereotyped behaviors. Repeated MA administration produced behavioral sensitization and LTP impairment in the hippocampal-mPFC pathways. The MA-induced impairment of hippocampal-mPFC LTP was prevented by the pretreatment of dopamine 1 (D1) but not dopamine 2 (D2) receptor antagonists, while D1 and D2 receptor antagonists attenuated the MA-induced stereotyped behaviors. These findings suggest that D1 receptors are crucial for the MA-induced deterioration of synaptic plasticity in the hippocampal-mPFC circuits. Impairment of LTP associated with D1 receptor dysfunction may underlie cognitive deficits in MA-dependent subjects.

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

“…Emerging evidence demonstrates that elevated endogenous BDNF is also required for the maintenance of high frequency stimulation-associated late-phase hippocampal LTP (Lu et al, 2008), suggesting that BDNF levels are low under normal conditions and are elevated by stimuli that enhance hippocampal activity. In this context, chronic methamphetamine exposure enhances baseline hippocampal CA1 activity, increases excitability of dentate gyrus neurons, and increases paired pulse facilitation, and these alterations result in occlusion of hippocampal LTP development (Criado et al, 2000, Onaivi et al, 2002, Ishikawa et al, 2005, Hori et al, 2010, Swant et al, 2010, North et al, 2013). Therefore, it can be hypothesized that methamphetamine induces the same neurobiological changes in the hippocampus that are required for generation and maintenance of hippocampal synaptic activity and additional activation as a consequence of tetanic stimulations in the hippocampus of methamphetamine experienced animals may not produce LTP (Hope, 1998, Schulz et al, 1999, Onaivi et al, 2002).…”

Medial prefrontal cortex stimulation modulates the processing of conditioned fear

“…Hallett (2000) and Hoogendam et al (2010) propose that rTMS influences the consolidation of learning by modifying excitatory synaptic efficacy or neuronal synchrony. By comparing high- and low-frequency stimulation in mice using an offline approach, successful extinction learning was associated with long-term potentiation (LTP) while long-term depression (LTD) resulted in the return of conditioned fear (Herry and Garcia, 2002). High-frequency rTMS over 10 consecutive days in rats was further associated with a lasting increase of prelimbic levels of the brain-derived neurotrophic factor (BDNF), a neuroplasticity marker involved in LTP (Gersner et al, 2011).…”

A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition

“…3). As depressed evoked potentials in the nucleus accumbens are correlated with increased dopamine activity both in vitro (Beurrier and Malenka, 2002;O'Donnell and Grace, 1998;Pennartz et al, 1992) and in vivo (Hunt et al, 2005), those results bring new light at a cellular level about how HbCpl lesions may induce cognitive deficits through increase of dopamine release (Chuhan and Taukulis, 2005;Ishikawa et al, 2005;LeivaSantana and Alvarez-Sauco, 2006;Robbins, 2002).…”