Table 3

Overview of studies in which pharmacological agents were administered systemically with the aim of inducing reactivation-dependent amnesia for contextual fear memories in rodents, as identified by the systematic review

Target/functionDrugSubjectsAdministration routeDose (/kg)Amnesic effect obtained?
Protein synthesis inhibitors
 DNA and protein synthesis interferenceAnisomycinMicei.p.75 mg+
Micei.p.150 mg+ and +/−1, 3
Micei.p.225 mg+/−
Mices.c.50 mg*
Ratsi.p.50 mg+
 mRNA translocation interferenceCycloheximideRatsi.p.2.2 mg+
Receptor antagonists
 Oxytocin receptorAtosibanRatsi.p.0.001–1 mg-
 Adenosine receptorCaffeineRatsi.p.20 mg+/−1
 GABAA-R (partial agonist)FlumazenilRatsi.p.1 mg+
 NMDA-RMK-801Micei.p.0.03 mg+
  Micei.p.0.06 mg+
  Micei.p.0.1 mg+ and +/−
  Micei.p.0.12 mg+
  Ratsi.p.0.1 mg+ and +/−3 and -
 Opioid receptorNaloxoneRatsi.p.3 mg+/−3
 β-Adrenergic receptorPropranololMicei.p.10 mg- and +/−
Ratsi.p.2 mg-
Ratsi.p.5 mg+ and -
Ratsi.p.10 mg+ and -
 Dopamine D1/D5 receptorSCH23390Ratsi.p.0.1 mg-
 CB1-R (partial agonist)SR141716AMicei.p.1–10 mg-
 Histamine H3-R (inverse agonist)ThioperamideMicei.p.2.5–30 mg-
PitolisantMicei.p.1.25–20 mg-
Receptor agonists
 GABAA-RBetulin (BE)Ratsoral2 mg-
Betulinic Acid (BA)Ratsoral2 mg-
BE + BARatsoral2 mg+
EthanolRatsi.p.0.5/1/1.5 mg+/−4
Souroubea sympetalaRatsoral8/25/75 mg+/−4*
 α2-Adrenergic receptorClonidineMicei.p.0.3 mg+/−1
  Ratsi.p.0.1 mg-
  Ratsi.p.0.3 mg+
 μ-Opioid receptorMorphineRatss.c.7.5 mg*
 NOP receptorRo 65–6570Micei.p.0.1/1 mg+/−4
AT-403Micei.p.0.03/0.1 mg+/−4
Benzodiazepines
 GABAA receptor agonistDiazepamRatsoral1/2 mg+
 GABAA receptor (allosteric modulator)MidazolamRatss.c.1 mg+
Ratsi.p.1 mg+ and -
Ratsi.p.1.5 mg+ and - and +/−1, 2, 3
Ratsi.p.1/1.5/3 mg+/−4
Ratsi.p.2 mg+
Ratsi.p.3 mg+ and - and +/−3
Cannabinoids
 Indirect potentiation of CB1-R-mediated transmissionCBDRatsi.p.1 mg+/−
Ratsi.p.3 mg+
Ratsi.p.10 mg+/−
Ratsi.p.30 mg+
Ratsoral50 mg+
 Activation of cannabinoid systemCannabis plant extracts (after
isolation of THC and CBD)		Ratsoral43 mg+
 CB1-R agonistTHCRatsoral5 mg-
Ratsi.p.0.1/0.3/1/10 mg+/−4
Intracellular molecule inhibitors
 DNA ligases and polymerasesAra-CMicei.p.1000 mg-
 GSK-3AR-A014418Micei.p.30 mg+
 NF-κBDDTCRatsi.p.200 mg+
 11β-hydroxylaseMetyraponeRatsi.p.75 mg-
 PARP-1Tiq-AMicei.p.0.5 mg+
Other
 HormoneCorticosteroneRatsi.p.1/3/10 mg+/−1, 4
 PeptideGRPRatsi.p.10 nmol+
 Bacterial toxinLipopolysaccharidesMicei.p.125 μg+
 NE-DA reuptake inhibitorMethylphenidateRatsi.p.3/10 mg-
 DA reuptake inhibitorModafinilMicei.p.200 mg+
 AMPA receptor potentiatorPEPAMicei.p.30 mg-
 Glutamatergic system blockerRiluzoleRatss.c.0.1/0.3/1/3 mg+/−4

  • Additional details for each study, including PubMed ID, strain, duration of the reactivation session (ranging from 30 s to 10 min), time of drug administration, and time between training and reactivation session (ranging from 1 to 36 d), are available at https://osf.io/x2pkq/. Ara-C = 1-β-D-arabinofuranosylcytosine triphosphate; CBD = cannabidiol; DA = dopamine; DDTC = diethyldithiocarbamate; GRP = gastrin releasing peptide; NE = norepinephrine; PEPA = 4-[2-(phenylsulfonylamino)ethylthio]−2,6-difluorophenoxyacetamide; s.c. = subcutaneous; THC = Δ9-tetrahydro-cannabinol; + = at least one study reported a statistically significant amnestic effect; * = amnestic effect was found to be transient; - = at least one study reported a non-significant effect; +/− = at least one study observed that the amnestic effect occurred under some conditions:

  • ↵1 depending on training parameters (e.g., shock intensity).

  • 2 depending on memory age.

  • ↵3 depending on reactivation duration.

  • ↵4 depending on drug dose.